Head and Neck Cancers - Molecular Biology


Literature Analysis

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Tag cloud generated 29 August, 2019 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (52)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

CDKN2A 9p21.3 ARF, MLM, P14, P16, P19, CMM2, INK4, MTS1, TP16, CDK4I, CDKN2, INK4A, MTS-1, P14ARF, P19ARF, P16INK4, P16INK4A, P16-INK4A Prognostic
-CDKN2A Mutations in Head and Neck Cancer
GSTM1 1p13.3 MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b -GSTM1 and Head and Neck Cancers
PTGS2 1q31.1 COX2, COX-2, PHS-2, PGG/HS, PGHS-2, hCox-2, GRIPGHS -PTSG2 (COX2) and Head and Neck Squamous Carcinoma
GSTT1 22q11.23 -GSTT1 Polymorphisms and Head and Neck Cancer
NOTCH1 9q34.3 hN1, AOS5, TAN1, AOVD1 -NOTCH1 mutations in Head and Neck Cancers
ALDH2 12q24.12 ALDM, ALDHI, ALDH-E2 -ALDH2 and Head and Neck Cancers
SDHD 11q23.1 PGL, CBT1, CWS3, PGL1, QPs3, SDH4, cybS, CII-4 -SDHD and Head and Neck Cancers
SDHB 1p36.13 IP, SDH, CWS2, PGL4, SDH1, SDH2, SDHIP -SDHB and Head and Neck Cancers
MIR21 17q23.1 MIRN21, miR-21, miRNA21, hsa-mir-21 -MicroRNA miR-21 and Head and Neck Cancer
SDHC 1q23.3 CYBL, PGL3, QPS1, SDH3, CYB560 -SDHC and Head and Neck Cancers
TP63 3q28 AIS, KET, LMS, NBP, RHS, p40, p51, p63, EEC3, OFC8, p73H, p73L, SHFM4, TP53L, TP73L, p53CP, TP53CP, B(p51A), B(p51B) -TP63 and Head and Neck Cancers
XRCC3 14q32.33 CMM6 -XRCC3 and Head and Neck Cancers
ADH1B 4q23 ADH2, HEL-S-117 -ADH1B and Head and Neck Cancers
TIMP3 22q12.3 SFD, K222, K222TA2, HSMRK222 -TIMP3 and Head and Neck Cancers
NFIB 9p23-p22.3 CTF, NF1-B, NFI-B, NFIB2, NFIB3, NF-I/B, NFI-RED, HMGIC/NFIB -NFIB and Head and Neck Cancers
CTTN 11q13.3 EMS1 -CTTN and Head and Neck Cancers
VHL 3p25.3 RCA1, VHL1, pVHL, HRCA1 -VHL and Head and Neck Cancers
OGG1 3p25.3 HMMH, MUTM, OGH1, HOGG1 -OGG1 and Head and Neck Cancers
ADH1C 4q23 ADH3 -ADH1C and Head and Neck Cancers
CKAP4 12q23.3 p63, CLIMP-63, ERGIC-63 -CKAP4 and Head and Neck Cancers
CCNA1 13q13.3 CT146 -CCNA1 and Head and Neck Cancers
PGLS 19p13.11 6PGL, HEL-S-304 -PGLS and Head and Neck Cancers
LAMC2 1q25.3 B2T, CSF, EBR2, BM600, EBR2A, LAMB2T, LAMNB2 -LAMC2 and Head and Neck Cancers
EDNRB 13q22.3 ETB, ET-B, ETB1, ETBR, ETRB, HSCR, WS4A, ABCDS, ET-BR, HSCR2 -EDNRB and Head and Neck Cancers
CCR7 17q21.2 BLR2, EBI1, CCR-7, CD197, CDw197, CMKBR7, CC-CKR-7 -CCR7 and Head and Neck Cancers
SDHAF2 11q12.2 PGL2, SDH5, C11orf79 -SDHAF2 and Head and Neck Cancers
S100A2 1q21.3 CAN19, S100L -S100A2 and Head and Neck Cancers
SDHA 5p15.33 FP, PGL5, SDH1, SDH2, SDHF, CMD1GG -SDHA and Head and Neck Cancers
ERCC4 16p13.12 XPF, RAD1, FANCQ, XFEPS, ERCC11 -ERCC4 and Head and Neck Cancers
PLAU 10q22.2 ATF, QPD, UPA, URK, u-PA, BDPLT5 -PLAU and Head and Neck Cancers
FAT1 4q35.2 FAT, ME5, CDHF7, CDHR8, hFat1 -FAT1 and Head and Neck Cancers
TMEM127 2q11.2 -TMEM127 and Head and Neck Cancers
SLC5A8 12q23.1-q23.2 AIT, SMCT, SMCT1 -SLC5A8 and Head and Neck Cancers
MAGEB2 Xp21.2 DAM6, CT3.2, MAGE-XP-2 -MAGEB2 and Head and Neck Cancers
CIC 19q13.2 -CIC and Head and Neck Cancers
ADAM17 2p25 CSVP, TACE, NISBD, ADAM18, CD156B, NISBD1 -ADAM17 and Head and Neck Cancers
CCL19 9p13.3 ELC, CKb11, MIP3B, MIP-3b, SCYA19 -CCL19 and Head and Neck Cancers
MTHFD1 14q23.3 MTHFC, MTHFD -MTHFD1 and Head and Neck Cancers
CYP2A13 19q13.2 CPAD, CYP2A, CYPIIA13 -CYP2A13 and Head and Neck Cancers
CSMD1 8p23.2 PPP1R24 -CSMD1 and Head and Neck Cancers
LIMD1 3p21.31 -LIMD1 and Head and Neck Cancers
ING3 7q31.31 Eaf4, ING2, MEAF4, p47ING3 -ING3 and Head and Neck Cancers
CD3D 11q23.3 T3D, IMD19, CD3-DELTA -CD3D and Head and Neck Cancers
TMC6 17q25.3 EV1, EVER1, EVIN1, LAK-4P -TMC6 and Head and Neck Cancers
RNF213 17q25.3 ALO17, MYMY2, MYSTR, NET57, C17orf27, KIAA1618 -RNF213 and Head and Neck Cancers
RHOBTB2 8p21.3 DBC2 -RHOBTB2 and Head and Neck Cancers
TMC8 17q25.3 EV2, EVER2, EVIN2 -TMC8 and Head and Neck Cancers
SPECC1 17p11.2 NSP, CYTSB, HCMOGT1, HCMOGT-1 -SPECC1 and Head and Neck Cancers
MIR1271 5q35.2 MIRN1271, hsa-mir-1271 -MIRN1271 microRNA, human and Head and Neck Cancers
KLK10 19q13.41 NES1, PRSSL1 -KLK10 and Tongue Neoplasms
PCSK7 11q23.3 LPC, PC7, PC8, SPC7 -PCSK7 and Head and Neck Cancers

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications

Tomasovic-Loncaric C, Fucic A, Andabak A, et al.
Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk.
Anticancer Res. 2019; 39(8):4285-4289 [PubMed] Related Publications
BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC.
PATIENTS AND METHODS: Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry.
RESULTS: More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients.
CONCLUSION: More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.

Matsunaga N, Wakasaki T, Yasumatsu R, Kotake Y
Long Noncoding RNA,
Anticancer Res. 2019; 39(8):4073-4077 [PubMed] Related Publications
BACKGROUND/AIM: ANRIL is a long noncoding RNA located on INK4 locus, which encodes p15 and p16 that cause G
MATERIALS AND METHODS: Cells were transfected with siRNA oligonucleotides targeting ANRIL. Transfected cells were subjected to cell-cycle and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis.
RESULTS: Depletion of ANRIL increased p15 mRNA in FaDu cells, and p15 and p16 mRNA in CAL27 cells and inhibited proliferation of these cells. Cell cycle analysis showed that depletion of ANRIL caused arrest at the G

Vakili Saatloo M, Aghbali AA, Koohsoltani M, Yari Khosroushahi A
Akt1 and Jak1 siRNA based silencing effects on the proliferation and apoptosis in head and neck squamous cell carcinoma.
Gene. 2019; 714:143997 [PubMed] Related Publications
Based on Akt1 and Jak1 key roles in apoptosis and proliferation of many cancers, the aim of this study was to find a new gene therapy strategy by silencing of these main anti-apoptotic genes for HNSCC treatment. Cancerous HN5 and normal HUVEC cell lines were treated with Akt1 and Jak1 siRNAs alone or with each other combined with/without cisplatin. The MTS, flow cytometry, 4',6-diamidino-2-phenylindole staining, real-time PCR and ELISA methods were utilized in this study. The highest percentage of apoptosis was observed in the treatment of Jak1 siRNA/cisplatin group in cancerous HN5 cells (96.5%) where this treatment showed 12.84% apoptosis in normal HUVEC cell line. Cell viability reduced significantly to 64.57% after treatment with Akt1 siRNA in HN5 treated group. Knocking down Akt1 and Jak1 genes using siRNAs could increase levels of apoptosis and reduce proliferation rate in HNSCC indicating the powerful effects of these genes siRNAs with or without chemotherapeutic agents in HNSCC treatment. In conclusion, the combination of siRNA-mediated gene-silencing strategy can be considered as a valuable and safe approach for sensitizing cancer cells to chemotherapeutic agents thus proposed further studies regarding this issue to approve some siRNA based therapeutics for using in clinic.

Kutahyalioglu M, Nguyen HT, Kwatampora L, et al.
Genetic profiling as a clinical tool in advanced parathyroid carcinoma.
J Cancer Res Clin Oncol. 2019; 145(8):1977-1986 [PubMed] Related Publications
CONTEXT: Parathyroid carcinoma (PC) is a rare endocrine malignancy with no approved systemic therapies for unresectable locally invasive or distant metastatic disease. Understanding the molecular changes in advanced PC can provide better understanding of this disease and potentially help directing targeted therapy.
OBJECTIVE: To evaluate tumor-specific genetic changes using next-generation sequencing (NGS) panels.
DESIGN: All patients with advanced PC were tested for hot-spot panels using NGS panels including a 50-gene panel, a 409-gene panel if the standard 50-gene panel (Ion Torrent, Life Technology) was negative or a FoundationOne panel.
SETTING: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
PATIENTS OR OTHER PARTICIPANTS: 11 patients with advanced PC were selected to undergo molecular testing.
MAIN OUTCOME MEASURE(S): Genetic profiles of advanced PC.
RESULTS: Among the 11 patients, 4 patients had the 50-gene panel only, 6 had 409-gene panel after a negative 50-gene panel and 1 had FoundationOne. One patient who had 50-gene panel only also had his metastatic site (esophagus) of his tumor tested with FoundationOne. The most common mutations identified were in the PI3 K (PIK3CA, TSC1 and ATM) (4/11 patients) and TP53 (3/11) pathways. Genes not previously reported to be mutated in PC included: SDHA, TERT promoter and DICER1. Actionable mutations were found in 54% (6/11) of the patients.
CONCLUSIONS: Mutational profiling using NGS panels in advanced PC has yielded important potentially targetable genetic alterations. Larger studies are needed to identify commonly mutated genes in advanced PC patients. Development of novel therapies targeting these cellular pathways should be considered.

Zhang H, Yu Y, Zhang K, et al.
Targeted inhibition of long non-coding RNA H19 blocks anaplastic thyroid carcinoma growth and metastasis.
Bioengineered. 2019; 10(1):306-315 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
Long non-coding RNA H19 (H19) is highly expressed in cancers and is considered to highly correlate with the extent of malignant degree. The present study was performed to determine the expression levels of H19 in anaplastic thyroid carcinoma (ATC) tissues and the role of H19 in ATC 8505C cells

Zhong X, Huang G, Ma Q, et al.
Identification of crucial miRNAs and genes in esophageal squamous cell carcinoma by miRNA-mRNA integrated analysis.
Medicine (Baltimore). 2019; 98(27):e16269 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
Esophageal squamous cell carcinoma (ESCC) is a malignancy that severely threatens human health and carries a high incidence rate and a low 5-year survival rate. MicroRNAs (miRNAs) are commonly accepted as a key regulatory function in human cancer, but the potential regulatory mechanisms of miRNA-mRNA related to ESCC remain poorly understood.The GSE55857, GSE43732, and GSE6188 miRNA microarray datasets and the gene expression microarray datasets GSE70409, GSE29001, and GSE20347 were downloaded from Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using GEO2R. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network and functional modules were established using the STRING database and were visualized by Cytoscape. Kaplan-Meier analysis was constructed based on The Cancer Genome Atlas (TCGA) database.In total, 26 DEMs and 280 DEGs that consisted of 96 upregulated and 184 downregulated genes were screened out. A functional enrichment analysis showed that the DEGs were mainly enriched in the ECM-receptor interaction and cytochrome P450 metabolic pathways. In addition, MMP9, PCNA, TOP2A, MMP1, AURKA, MCM2, IVL, CYP2E1, SPRR3, FOS, FLG, TGM1, and CYP2C9 were considered to be hub genes owing to high degrees in the PPI network. MiR-183-5p was with the highest connectivity target genes in hub genes. FOS was predicted to be a common target gene of the significant DEMs. Hsa-miR-9-3p, hsa-miR-34c-3p and FOS were related to patient prognosis and higher expression of the transcripts were associated with a poor OS in patients with ESCC.Our study revealed the miRNA-mediated hub genes regulatory network as a model for predicting the molecular mechanism of ESCC. This may provide novel insights for unraveling the pathogenesis of ESCC.

Yoo SK, Song YS, Lee EK, et al.
Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer.
Nat Commun. 2019; 10(1):2764 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAF

Demin DE, Afanasyeva MA, Uvarova AN, et al.
Constitutive Expression of NRAS with Q61R Driver Mutation Activates Processes of Epithelial-Mesenchymal Transition and Leads to Substantial Transcriptome Change of Nthy-ori 3-1 Thyroid Epithelial Cells.
Biochemistry (Mosc). 2019; 84(4):416-425 [PubMed] Related Publications
The Q61R mutation of the NRAS gene is one of the most frequent driver mutations of thyroid cancer. Tumors with this mutation are characterized by invasion into blood vessels and formation of distant metastases. To study the role of this mutation in the growth of thyroid cancer, we developed a model system on the basis of thyroid epithelial cell line Nthy-ori 3-1 transduced by a lentiviral vector containing the NRAS gene with the Q61R mutation. It was found that the expression of NRAS(Q61R) in thyroid epithelial cells has a profound influence on groups of genes involved in the formation of intercellular contacts, as well as in processes of epithelial-mesenchymal transition and cell invasion. The alteration in the expression of these genes affects the phenotype of the model cells, which acquire traits of mesenchymal cells and demonstrate increased ability for survival and growth without attachment to the substrate. The key regulators of these processes are transcription factors belonging to families SNAIL, ZEB, and TWIST, and in different types of tumors the contribution of each individual factor can vary greatly. In our model system, phenotype change correlates with an increase in the expression of SNAIL2 and TWIST2 factors, which indicates their possible role in regulating invasive growth of thyroid cancer with the mutation of NRAS(Q61R).

Rendleman MC, Buatti JM, Braun TA, et al.
Machine learning with the TCGA-HNSC dataset: improving usability by addressing inconsistency, sparsity, and high-dimensionality.
BMC Bioinformatics. 2019; 20(1):339 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
BACKGROUND: In the era of precision oncology and publicly available datasets, the amount of information available for each patient case has dramatically increased. From clinical variables and PET-CT radiomics measures to DNA-variant and RNA expression profiles, such a wide variety of data presents a multitude of challenges. Large clinical datasets are subject to sparsely and/or inconsistently populated fields. Corresponding sequencing profiles can suffer from the problem of high-dimensionality, where making useful inferences can be difficult without correspondingly large numbers of instances. In this paper we report a novel deployment of machine learning techniques to handle data sparsity and high dimensionality, while evaluating potential biomarkers in the form of unsupervised transformations of RNA data. We apply preprocessing, MICE imputation, and sparse principal component analysis (SPCA) to improve the usability of more than 500 patient cases from the TCGA-HNSC dataset for enhancing future oncological decision support for Head and Neck Squamous Cell Carcinoma (HNSCC).
RESULTS: Imputation was shown to improve prognostic ability of sparse clinical treatment variables. SPCA transformation of RNA expression variables reduced runtime for RNA-based models, though changes to classifier performance were not significant. Gene ontology enrichment analysis of gene sets associated with individual sparse principal components (SPCs) are also reported, showing that both high- and low-importance SPCs were associated with cell death pathways, though the high-importance gene sets were found to be associated with a wider variety of cancer-related biological processes.
CONCLUSIONS: MICE imputation allowed us to impute missing values for clinically informative features, improving their overall importance for predicting two-year recurrence-free survival by incorporating variance from other clinical variables. Dimensionality reduction of RNA expression profiles via SPCA reduced both computation cost and model training/evaluation time without affecting classifier performance, allowing researchers to obtain experimental results much more quickly. SPCA simultaneously provided a convenient avenue for consideration of biological context via gene ontology enrichment analysis.

Imai A, Mochizuki D, Misawa Y, et al.
DNA Cell Biol. 2019; 38(7):678-687 [PubMed] Related Publications
Staging and pathological grading systems are convenient, but imperfect predictors of recurrence of head and neck squamous cell carcinoma. Therefore, to identify potential alternative prognostic markers, we investigated the methylation status of the promoter of Sal-like protein 2 (

Stadler TM, Morand GB, Rupp NJ, et al.
[Benefits of Molecular Analyses in Thyroid Carcinoma].
Praxis (Bern 1994). 2019; 108(8):535-540 [PubMed] Related Publications
Benefits of Molecular Analyses in Thyroid Carcinoma

Huang SJ, Tseng YK, Lo YH, et al.
Association of
Anticancer Res. 2019; 39(6):2891-2902 [PubMed] Related Publications
BACKGROUND/AIM: Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC.
MATERIALS AND METHODS: This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method.
RESULTS: Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype.
CONCLUSION: We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect.

Punda A, Bedeković V, Barić A, et al.
Acta Clin Croat. 2018; 57(4):646-652 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
- The purpose of this study was to analyze the possible prognostic value of RET mutation in papillary thyroid carcinoma and its incidence in the past few decades in our population, due to the increasing incidence of papillary thyroid carcinoma. The present study included 180 patients operated for papillary thyroid carcinoma. The clinical and histopathologic characteristics were analyzed. Paraffin sections of the selected histologic slides were cut again and immunohistochemically stained by the Clone 3F8 P (HIER) from Novocastra (Vision Bio Systems Europe, Newcastle upon Tyne, UK) monoclonal antibody to RET oncoprotein. Univariate analysis indicated sex (p=0.01), histologic subtype (p=0.075) and capsular invasion (p=0.010) to be statistically significant predictors of lymph node metastases, whereas age (p=0.796), tumor size (p=0.556) and intraglandular dissemination (p=0.131) showed no such correlation. The presence of RET mutation (p=0.704) was not a statistically significant predictor of the tumor metastasizing potential. RET mutation (p=0.500) showed no statistically significant correlation with papillary thyroid carcinoma classifed into prognostic groups according to clinicopathologic features either. RET mutation was detected in 30% of 180 papillary thyroid carcinomas. This is the first large study demonstrating that RET mutation incidence in papillary thyroid carcinoma in Croatian population is consistent with the classic distribution of sporadic cases, despite the increased prevalence of papillary thyroid carcinoma in the past few decades.

Yan Q, Chen T, Yang H, et al.
The Effect of FERMT1 Regulated by miR-24 on the Growth and Radiation Resistance of Esophageal Cancer.
J Biomed Nanotechnol. 2019; 15(3):621-631 [PubMed] Related Publications
The present study addresses the role and underlying mechanism of FERMT1 in the development of esophageal cancer (EC). High level of FERMT1 expression was found in human EC tissues and was significantly correlated with poor overall survival. Overexpression of FERMT1 by a lentiviral vector markedly promoted EC cell proliferation and radiation resistance

Zhang P, Lu X, Shi Z, et al.
miR-205-5p regulates epithelial-mesenchymal transition by targeting PTEN via PI3K/AKT signaling pathway in cisplatin-resistant nasopharyngeal carcinoma cells.
Gene. 2019; 710:103-113 [PubMed] Related Publications
Epithelial-mesenchymal transition (EMT) symbolizes the predominant program of advanced-stage cancer, it is critical in cancer progression, metastasis, and chemotherapy resistance. In this study, the metastatic properties of nasopharyngeal carcinoma (NPC) cells were evaluated by morphological examination, wound healing assay, migration and invasion assay. Western blotting and qRT-PCR were used to ascertain the expression of markers which were associated with EMT. The effects of miR-205-5p on invasion, migration, EMT and proliferation of NPC cells were evaluated and the molecular mechanisms of their interaction were explored. In this study, we manifested firstly that the expression of miR-205-5p in cisplatin-resistant NPC cell line HNE1/DDP was obviously up-regulated than that in its parental cell line HNE1. Then we analyzed the specific role of miR-205-5p through functional assays by transfecting specific mimics and inhibitors. The results indicated that low expression of miR-205-5p restrained EMT progression of HNE1/DDP cells. Further studies on the mechanism of miR-205-5p manifested that PTEN was a downstream candidate gene of miR-205-5p, down-regulated PTEN expression could counteract the effect of miR-205-5p inhibitors, and the regulation of EMT by miR-205-5p on HNE1/DDP cells depended on the PI3K/AKT signaling pathway. Overall, our results indicated that miR-205-5p was targeting PTEN to regulate EMT through the PI3K/AKT pathway. This study will supply a new treatment target for advanced NPC.

Chen S, Li Z, Zhou L, Zhang Y
Nan Fang Yi Ke Da Xue Xue Bao. 2019; 39(5):554-560 [PubMed] Related Publications
OBJECTIVE: To investigate the effect of sputum ubiquitin ligase (Cbl-b) gene known-down on the cytotoxicity of H9 T lymphocytes against human laryngeal squamous cancer Hep-2 cells and explore the underlying mechanism.
CONCLUSIONS: Cbl-b gene silencing effectively enhances the killing effect of H9 T lymphocytes against Hep-2 cells

Chen X, Cai S, Wang L, et al.
Analysis of the function of MAGE-A in esophageal carcinoma by bioinformatics.
Medicine (Baltimore). 2019; 98(21):e15774 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
BACKGROUND: Melanoma-associated antigen-A (MAGE-A) was recognized as high-expressed in many solid tumors including esophageal carcinoma (EC), nevertheless, was reported to be low/not-expressed in normal tissues. Thus, it was considered as an extraordinary appropriate target for treatment especially in immunotherapy. Therefore, it demanded more detail knowledge on the precise function of MAGE-A.
METHODS: In this study, we used the data from the Cancer Genome Atlas dataset (TCGA-ESCA) to analyze the expression and survival for MAGE A3/4/11 (the subtype of MAGE-A) using the online tool of UALCAN. Furthermore, the high-throughput sequencing data of the patients with esophageal squamous-cell carcinoma (ESCC) from TCGA dataset were performed to analyze the correlation test, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of MAGE A3/4/9/11 using LinkeDomics (online tool) and ClueGO (inner software of Cytoscape). Finally, relative gene expressions of MAGE A3/4/9/11 were verified by quantitative real-time PCR (q-PCR) in the patients with EC.
RESULTS: MAGE A3/4/11 was high-expressed in tissues of patients with ESCC, and there was no difference in survival time for patients between the high-expressed with the low/medium-expressed. The Go enrichment analysis showed that the 4 MAGE-A subtypes (MAGE-A3/4/9/11) were enriched in the regulation of the adaptive immune response, translational initiation, interleukin-4 production, response to type I interferon, and skin development, respectively. The KEGG results showed that they were enriched in T cell receptor signaling pathway (MAGE-A3), Th1 and Th2 differentiation, antigen processing and presentation (MAGE-A4), cytokine-cytokine receptor interaction (MAGE-A9), and chemokine signaling pathway (MAGE-A11).
CONCLUSION: MAGE A3/4/9/11 was high-expressed in EC, and were enrolled in the regulation of immune response. They may consider as candidate immune target for EC treatment and provided the messages for further research in the function of MAGE-A.

Yang L, Wei W, Zhou L, et al.
High/positive expression of ERCC1 predicts poor treatment response and survival prognosis in nasopharyngeal carcinoma: A systematic meta-analysis from 21 studies.
Medicine (Baltimore). 2019; 98(21):e15641 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) protein is a member of the nucleotide excision repair (NER) system, which plays an important role in DNA damage repair. Recently, its predictive and prognostic value in nasopharyngeal carcinoma (NPC) has been investigated by several studies. However, their results remain controversial.
OBJECTIVES: In an attempt to address this issue, we conducted the present comprehensive meta-analysis.
DATA SOURCES: Studies published until November 2017 were searched. Finally, total 21 literatures involving 22 cohorts and 2921 NPC patients fulfilled the inclusion criteria.
RESULTS: The pooled results showed that high/positive expression of ERCC1 predicted poor objective response rate (ORR) [odds ratio (OR) = 2.83; 95% confidence interval (CI) = 2.11-3.80; P <.001], overall survival (OS) [hazard ratio (HR) = 1.77; 95% CI = 1.48-2.12; P <.001], and disease-free survival (DFS) (HR = 1.60; 95% CI = 1.43-1.79; P <.001) in NPC. Low heterogeneity was detected among these studies (ORR: I = 0.0%, P = .776; DFS: I = 38.7%, P = .148; OS: I = 0.0%; P = .530). The results of sensitivity analyses and publication bias verified the reliability of our findings.
CONCLUSIONS: This study suggested ERCC1 as a potential predictive and prognostic biomarker for the treatment response and survival prognosis of NPC patients.

Nowinska K, Ciesielska U, Piotrowska A, et al.
MCM5 Expression Is Associated With the Grade of Malignancy and Ki-67 Antigen in LSCC.
Anticancer Res. 2019; 39(5):2325-2335 [PubMed] Related Publications
BACKGROUND/AIM: The minichromosome maintenance proteins (MCMs) may be potential biomarkers of cancer cell proliferation. They are essential to initiate DNA replication. The aim of the study was to investigate the level of MCM5 expression in benign lesions (BLs) and laryngeal squamous cell cancer (LSCC).
MATERIALS AND METHODS: Immunohistochemical (IHC) analysis was carried out on 83 LSCCs and 10 BLs. Western-blot, immunofluorescence analysis (IF) and real-time PCR (RT-PCR) were performed using HEp-2 cancer cells and HaCaT keratinocytes.
RESULTS: The expression of MCM5 was higher in LSCC than in the BLs (p<0.0001) and was higher in subsequent malignancies of LSCC. Positive correlations were demonstrated between the expression levels of MCM5 and the Ki-67 antigen. In vitro studies have confirmed that the expression of MCM5 is elevated in cancer cells.
CONCLUSION: MCM5 protein may be used as a potential marker of cancer cell proliferation in LSCC.

Bao XD, Lin LS, Chen F, et al.
[Association of single nucleotide polymorphisms of
Zhonghua Yu Fang Yi Xue Za Zhi. 2019; 53(5):480-485 [PubMed] Related Publications

Xiao Y, Li H, Yang LL, et al.
The Expression Patterns and Associated Clinical Parameters of Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 and Transmembrane and Immunoglobulin Domain Containing 2 in Oral Squamous Cell Carcinoma.
Dis Markers. 2019; 2019:5421985 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) and transmembrane and immunoglobulin domain containing 2 (TMIGD2) are new immune checkpoint molecules of the B7:CD28 family; however, little research has been performed on these immune checkpoint molecules. In this study, we used oral squamous cells carcinoma (OSCC) tissue microarrays and immunohistochemistry methods to investigate the expression patterns of HHLA2 and TMIGD2 in OSCC. After comparing the HHLA2 and TMIGD2 expression levels in OSCC, dysplasia, and mucosa, we found increased HHLA2 expression in OSCC and dysplasia, while the TMIGD2 expression was decreased in OSCC and dysplasia. Using the Kaplan-Meier method and log-rank test, we found that higher HHLA2 or TMIGD2 expression levels in OSCC indicate poor prognosis. Furthermore, two-tailed Pearson's statistical analysis revealed that the HHLA2 expression levels in OSCC, dysplasia, and mucosa were positively correlated with the T cell immunoglobulin and mucin-domain containing-3 (TIM3), lymphocyte-activation gene 3 (LAG3), B7 homolog 3 protein (B7-H3), B7 homolog 4 protein (B7H4), and V-domain Ig suppressor of T cell activation (VISTA) levels, while the TMIGD2 expression levels in OSCC, dysplasia, and mucosa were inversely correlated with the TIM3, LAG3, and B7H3 levels. Our current study demonstrates that HHLA2 may serve as an immune target for OSCC therapy and that the TMIGD2 expression level in OSCC could forecast patient prognosis.

Zhou Y, Yang R, Ma G
[YAP1 knockdown suppresses the proliferation, migration and invasion of human nasopharyngeal carcinoma cells].
Nan Fang Yi Ke Da Xue Xue Bao. 2019; 39(3):286-291 [PubMed] Related Publications
OBJECTIVE: To investigate the effects of Yes-associated protein 1 (YAP1) knockdown on the proliferation, migration and invasion in human nasopharyngeal carcinoma (NPC) cells.
METHODS: We detected the expression of YAP1 mRNA and protein in different NPC cell lines and an immortalized nasopharyngeal epithelial cell line using RT-PCR and Western blotting. Two YAP1-targeting small interfering RNAs (siRNA) were transfected into NPC cell lines S26 and S18, and the knockdown efficiency was confirmed by RT-PCR and Western blotting. The effect of YAP1 knockdown on the proliferation of the NPC cells was determined by cell counting and colony formation assay; wound healing assay and Transwell assay were used to analyze the changes in the cell migration and invasion abilities in each group. Western blotting was used to analyze the changes in the expressions of c-myc, E-cadherin, N-cadherin and vimentin in the NPC cells after YAP1 knockdown.
RESULTS: YAP1 was highly expressed in the NPC cell lines. Compared with the negative control group, the NPC cell lines with YAP1 knockdown showed significantly lowered YAP1 expressions at both the mRNA and protein levels (

Rubinstein JC, Nicolson NG, Ahuja N
Next-generation Sequencing in the Management of Gastric and Esophageal Cancers.
Surg Clin North Am. 2019; 99(3):511-527 [PubMed] Related Publications
Next-generation sequencing has enabled genome-wide molecular profiling of gastric and esophageal malignancies at single-nucleotide resolution. The resultant genomic profiles provide information about the specific oncogenic pathways that are the likely driving forces behind tumorigenesis and progression. The abundance of available genomic data has immense potential to redefine management paradigms for these difficult disease processes. The ability to capitalize on the information provided through high-throughput sequencing technologies will define cancer care in the coming decades and could shift the paradigm from current stage-based, organ-specific treatments toward tailored regimens that target the specific culprit pathways driving individual tumors.

Pennathur A, Godfrey TE, Luketich JD
The Molecular Biologic Basis of Esophageal and Gastric Cancers.
Surg Clin North Am. 2019; 99(3):403-418 [PubMed] Related Publications
Esophageal cancer and gastric cancer are leading causes of cancer-related mortality worldwide. In this article, the authors discuss the molecular biology of esophageal and gastric cancer with a focus on esophageal adenocarcinoma. They review data from The Cancer Genome Atlas project and advances in the molecular stratification and classification of esophageal carcinoma and gastric cancer. They also summarize advances in microRNA, molecular staging, gene expression profiling, tumor microenvironment, and detection of circulating tumor DNA. Finally, the authors summarize some of the implications of understanding the molecular basis of esophageal cancer and future directions in the management of esophageal cancer.

Censi S, Barollo S, Grespan E, et al.
Prognostic significance of TERT promoter and BRAF mutations in TIR-4 and TIR-5 thyroid cytology.
Eur J Endocrinol. 2019; 181(1):1-11 [PubMed] Related Publications
Objective: Follicular-derived thyroid cancers generally have a good prognosis, but in a minority of cases, they have an aggressive behavior and develop distant metastases, with an increase in the associated mortality. None of the prognostic markers currently available prior to surgery can identify such cases.
Methods: TERT promoter and BRAF gene mutations were examined in a series of 436 consecutive TIR-4 and TIR-5 nodes referred for surgery. Follow-up (median: 59 months, range: 7-293 months) was available for 384/423 patients with malignant nodes.
Results: TERT promoter and BRAF mutations were detected in 20/436 (4.6%) and 257/434 thyroid nodules (59.2%), respectively. At the end of the follow-up, 318/384 patients (82.8%) had an excellent outcome, 48/384 (12.5%) had indeterminate response or biochemical persistence, 18/384 (4.7%) had a structural persistence or died from thyroid cancer. TERT promoter mutations correlated with older age (P < 0.0001), larger tumor size (P = 0.0002), oxyntic and aggressive PTC variants (P = 0.01), higher tumor stages (P < 0.0001), distant metastases (<0.0001) and disease outcome (P < 0.0001). At multivariate analysis, TERT promoter mutation was not an independent predictor of disease outcome. TERT promoter mutation- (OR: 40.58; 95% CI: 3.06-539.04), and N1b lymph node metastases (OR: 40.16, 95% CI: 3.48-463.04) were independent predictors of distant metastases. BRAF mutation did not predict the outcome, and it correlated with a lower incidence of distant metastases (P = 0.0201).
Conclusions: TERT promoter mutation proved an independent predictor of distant metastases, giving clinicians the chance to identify many of the patients who warranted more aggressive initial treatment and closer follow-up.

Su W, Wang Y, Wang F, et al.
Hsa_circ_0005379 regulates malignant behavior of oral squamous cell carcinoma through the EGFR pathway.
BMC Cancer. 2019; 19(1):400 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
BACKGROUND: Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy with a high incidence worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a vital role in modulating tumor development. However, the mechanism of circRNA action in human OSCC remains largely unknown.
METHODS: By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The effect of circRNA hsa_circ_0005379 on OSCC tissues and cell lines was monitored by qRT-PCR, Transwell assay, flow cytometry, and western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival.
RESULTS: We found that circRNA hsa_circ_0005379 expression is significantly lower in OSCC tissue compared to paired non-cancerous matched tissue and is associated with tumor size and differentiation. Overexpression of hsa_circ_0005379 effectively inhibits migration, invasion, and proliferation of OSCC cells in vitro and suppresses OSCC growth in nude mice in vivo. Mechanistic studies revealed that hsa_circ_0005379 may be involved in the regulation of the epidermal growth factor receptor (EGFR) pathway. Furthermore, we found that high expression of hsa_circ_0005379 could significantly enhance the sensitivity of OSCC to the cetuximab drug.
CONCLUSIONS: Our findings provide evidence that hsa_circ_0005379 regulates OSCC malignancy and may be a new therapeutic target for OSCC treatment.

Yin X, Yang W, Xie J, et al.
HOTTIP Functions as a Key Candidate Biomarker in Head and Neck Squamous Cell Carcinoma by Integrated Bioinformatic Analysis.
Biomed Res Int. 2019; 2019:5450617 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
Background: Accumulating evidence has demonstrated the pivotal role of long noncoding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks for predicting survival and evaluating prognosis in cancer patients. However, the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains unclear, and prognostic biomarkers for HNSCC are still lacking.
Methods: A total of 546 RNA sequencing profiles of HNSCC patients with clinical outcome data were obtained from the Cancer Genome Atlas (TCGA) database, providing a large sample of RNA sequencing data. From these, 71 Long noncoding RNAs lncRNAs, 8 microRNAs (miRNAs), and 16 messenger RNAs (mRNAs) were identified to construct a HNSCC-specific ceRNA network (fold change >2, P < 0.05). Univariate and multivariate Cox proportional regression models were used to assess independent indicators of prognosis. Then the expression of lncRNAs harboring prognostic value was validated in human HNSCC cell lines and tumor samples from our cohort and another two datasets from GEO (Gene Expression Omnibus) databases.
Results: As a result, a 3-mRNA signature and 6-lncRNA signature were identified. The six-lncRNA signature exhibited the highest prognostic value. Notably, in the six lncRNAs, HOTTIP showed the greatest prognostic value and was significantly correlated with clinical stage and histological grade of HNSCC patients. Furthermore, it was proved that HOTTIP was upregulated in HNSCC cell lines and cancerous tissues compared with corresponding normal cell lines and normal tissues. Functional assessment analysis revealed that HOTTIP might play a key role in the oncogenesis and progression of HNSCC.
Conclusion: The present study deepened our understanding of the ceRNA-related regulatory mechanism in the pathogenesis of HNSCC and identified candidate prognostic biomarkers for clinical outcome prediction in HNSCC. HOTTIP may function as a key candidate biomarker in HNSCC and serve as a prognostic marker for HNSCC patients.

Xing L, Zhang X, Tong D
Systematic Profile Analysis of Prognostic Alternative Messenger RNA Splicing Signatures and Splicing Factors in Head and Neck Squamous Cell Carcinoma.
DNA Cell Biol. 2019; 38(7):627-638 [PubMed] Related Publications
Head and neck squamous cell carcinoma (HNSC) is a common malignancy with high mortality and poor prognosis. Alternative splicing (AS) is a transcriptional regulation mechanism that generates multiple transcripts from same genes, and aberrant AS signatures of cancers can be predictive for prognosis. We identified the survival-related AS events and splicing factors (SFs) from the RNA sequencing data and the corresponding clinical information of an HNSC cohort downloaded from The Cancer Genome Atlas (TCGA) and SpliceSeq. The independent prognostic predictors were assessed by Cox proportional regression analysis, and the regulatory network of SFs and AS events was analyzed by Spearman's test and constructed. A total of 4626 survival-related AS events in 3280 genes were identified, and most were protective factors. Among the different types of splicing events, exon skip was the most frequent. The prognostic models were constructed for each type of AS, and the area under the curve of the receiver operating characteristic curve of the combined prognostic model was 0.765, indicating good predictive performance. Finally, a correlation network between SF and AS events was constructed. We identified prognostic predictors based on AS events that stratified HNSC patients into the high- and low-risk groups, and revealed splicing networks that provide insights into the underlying mechanisms.

Soni S, Saroch MK, Chander B, et al.
MAPKAPK2 plays a crucial role in the progression of head and neck squamous cell carcinoma by regulating transcript stability.
J Exp Clin Cancer Res. 2019; 38(1):175 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
BACKGROUND: Head and neck squamous-cell carcinoma (HNSCC) ranks sixth among cancers worldwide. Though several molecular mechanisms of tumor initiation and progression of HNSCC are known, others remain unclear. Significance of p38/MAPKAPK2 (Mitogen-activated protein kinase-activated protein kinase-2) pathway in cell stress and inflammation is well established and its role in tumor development is being widely studied.
METHODS: We have elucidated the role of MAPKAPK2 (MK2) in HNSCC pathogenesis using clinical tissue samples, MK2-knockdown (MK2
RESULTS: In patient-derived tissue samples, we observed that MK2 is reproducibly overexpressed. Increased stability of cyclin-dependent kinase inhibitor 1B (p27), mitogen-activated protein kinase phosphatase-1 (MKP-1) transcripts and decreased half-life of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) transcripts in MK2
CONCLUSION: Altogether, MK2 is responsible for regulating the transcript stability and is functionally important to modulate HNSCC pathogenesis.

Li JY, Huang WX, Zhou X, et al.
Numb inhibits epithelial-mesenchymal transition via RBP-Jκ-dependent Notch1/PTEN/FAK signaling pathway in tongue cancer.
BMC Cancer. 2019; 19(1):391 [PubMed] Article available free on PMC after 19/07/2020 Related Publications
BACKGROUND: Oral cancer has been estimated as the sixth most frequent solid cancer all over the world, in which tongue squamous cell carcinoma (TSCC) is the most common type of oral cancers. However, the mechanism of TSCC metastasizing to lymph node and distant sites has not been completely understood.
METHODS: In this study, RT-qPCR method was used to detect the mRNA level of Numb, PTEN and Notch1 genes, as well as EMT-associated genes. Western blot assay was utilized to detect protein level of these genes. In addition, we determined cell proliferation by MTT assay and employed transwell invasion assay and wound healing assay to probe the abilities of invasion and migration, respectively. To investigate the role of PTEN, its inhibitor VO-Ohpic trihydrate was used to treat SCC-4 and CAL27 cells.
RESULTS: We found that Numb expression was downregulated in SCC-9 and CAL-27 cells compared to NHOK cells. Instead, Notch1 level in SCC-9 and CAL-27 cells were higher than that in NHOK cells. Furthermore, the results showed that Numb overexpression significantly suppressed proliferation, migration and invasion of SCC-9 and CAL-27 cells via regulating Notch1 signaling and EMT-related genes expression. By contrast, we observed that RBP-Jκ knockdown had an inhibitory role in proliferation, migration and invasion of SCC-9 and CAL-27 cells. In cells with Numb overexpression or RBP-Jκ knockdown, p-FAK and EMT-related genes were remarkably regulated.
CONCLUSIONS: Our findings provide new mechanism of understanding the metastasis of TSCC and help develop therapeutic strategies for treating tongue cancer.

Recurring Structural Abnormalities

Selected list of common recurrent structural abnormalities

Abnormality Type Gene(s)
del(13q) in Head and Neck CancersDeletion

This is a highly selective list aiming to capture structural abnormalies which are frequesnt and/or significant in relation to diagnosis, prognosis, and/or characterising specific cancers. For a much more extensive list see the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.

del(13q) in Head and Neck Cancers

Maestro R, Piccinin S, Doglioni C, et al.
Chromosome 13q deletion mapping in head and neck squamous cell carcinomas: identification of two distinct regions of preferential loss.
Cancer Res. 1996; 56(5):1146-50 [PubMed] Related Publications
Heal and neck squamous cell carcinomas show frequent cytogenetic alterations involving the long arm of chromosome 13. To define the extent of 13q deletions and to identify the minimal areas of chromosome loss, 48 primary squamous cell carcinomas of the head and neck were analyzed for loss of heterozygosity using 11 different polymorphic loci. About 67% of the tumors displayed loss of genetic material at 13q. Most of the cases showed loss of the entire long arm of the chromosome. However, the presence of partial deletions in 10 cases provided evidence of the existence of two preferential sites of chromosome loss at 13q32-ter and 13q14.2-q14.3. The colocalization of the 13q14 minimal region of deletion with the retinoblastoma (RB) gene, which has been proposed as an oncosuppressor in diverse tumor types, prompted us to verify the involvement of this gene in the development of head and neck cancer. No significant variation in RB protein or RB mRNA expression was detected, thus excluding a role for such a gene in the genesis of this type of tumor. Taken together, our data suggest the existence of two new tumor suppressor genes (one close to and one distal to RB), which play a role in the development and/or progression of head and neck squamous cell carcinomas.

Gupta VK, Schmidt AP, Pashia ME, et al.
Multiple regions of deletion on chromosome arm 13q in head-and-neck squamous-cell carcinoma.
Int J Cancer. 1999; 84(5):453-7 [PubMed] Related Publications
Several lines of evidence suggest that the progression of head-and-neck squamous-cell carcinoma (HNSCC) involves inactivation of at least one and possibly several tumor-suppressor genes on the long arm of chromosome 13. The fact that neither Rb1 nor BRCA2 appears to be inactivated in the majority of head-and-neck cancers suggests that novel tumor-suppressor genes are involved. We have used microsatellite repeat polymorphisms and PCR to detect several distinct minimal regions of deletion on 13q in supraglottic and oral squamous-cell carcinomas. One region maps to 13q34, the second to 13q14.3 and a potential third region, not reported in previous studies, maps to 13q12.1. Overall, 69% of the 145 tumors examined demonstrated allelic loss at one or more loci on 13q. We investigated whether a novel suppressor candidate mapping to 13q14. 3-q21, leukemia-associated gene 1, might also be involved in the progression of squamous-cell carcinomas. Multiplexed PCR revealed homozygous deletion of leu1 in one oral cavity tumor. This suggests that this gene or one nearby may be the actual target of deletions in this region of the chromosome arm.

Sanchez-Cespedes M, Okami K, Cairns P, Sidransky D
Molecular analysis of the candidate tumor suppressor gene ING1 in human head and neck tumors with 13q deletions.
Genes Chromosomes Cancer. 2000; 27(3):319-22 [PubMed] Related Publications
The candidate tumor-suppressor gene ING1 encodes p33(ING1), a nuclear protein which physically interacts with TP53. It has been shown that p33(ING1) acts in the same biochemical pathway as TP53, leading to cell growth inhibition. Interestingly, a rearrangement of the ING1 gene was found in a neuroblastoma cell line, supporting its involvement in tumor development. Because ING1 resides on the long arm of chromosome 13 (13q34) (a region frequently deleted in many tumor types), we sought to characterize its role in head and neck squamous-cell carcinoma (HNSCC). We first analyzed 44 primary tumors for loss of heterozygosity (LOH) at 13q, using four widely spaced microsatellite markers (13q14, 13q14.3-q22, 13q22, and 13q34). Twenty (48%) of the tumor samples showed LOH in all of the informative markers tested, including D13S1315 at 13q34. Two of the tumors displayed partial losses restricted to one marker (D13S118 at 13q14 in tumor 1164, and D13S135 at 13q14.3-q22 in tumor 1398). We then determined the genomic structure of the ING1 gene and sequenced the entire coding region in 20 primary tumors showing 13q LOH and in five head and neck cancer cell lines. A single germline polymorphism was detected in 10 of the tumors analyzed (T to C change) located 110 nucleotides upstream of the starting methionine. No somatic mutations were found in any of the samples, suggesting that ING1 is not a tumor suppressor gene target in head and neck cancer. Genes Chromosomes Cancer 27:319-322, 2000.

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