Endometrial Cancer


Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

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

Mutated Genes and Abnormal Protein Expression (41)

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'.

PTEN 10q23.31 BZS, DEC, CWS1, GLM2, MHAM, TEP1, MMAC1, PTEN1, 10q23del -PTEN mutations in Endometrial Cancer
TP53 17p13.1 P53, BCC7, LFS1, TRP53 -TP53 Mutations in Endometrial Cancer
MSH6 2p16 GTBP, HSAP, p160, GTMBP, HNPCC5 -MSH6 and Endometrial Cancer
PIK3CA 3q26.32 MCM, CWS5, MCAP, PI3K, CLOVE, MCMTC, PI3K-alpha, p110-alpha -PIK3CA and Endometrial Cancer
ARID1A 1p36.11 ELD, B120, CSS2, OSA1, P270, hELD, BM029, MRD14, hOSA1, BAF250, C1orf4, BAF250a, SMARCF1 -ARID1A and Endometrial Cancer
JAZF1 7p15.2-p15.1 TIP27, ZNF802 -JAZF1 and Endometrial Cancer
ESR1 6q25.1-q25.2 ER, ESR, Era, ESRA, ESTRR, NR3A1 -ESR1 and Endometrial Cancer
CYP1B1 2p22.2 CP1B, GLC3A, CYPIB1, P4501B1 -CYP1B1 and Endometrial Cancer
L1CAM Xq28 S10, HSAS, MASA, MIC5, SPG1, CAML1, CD171, HSAS1, N-CAML1, NCAM-L1, N-CAM-L1 -L1CAM and Endometrial Cancer
SUZ12 17q11.2 CHET9, JJAZ1 -SUZ12 and Endometrial Cancer
YWHAE 17p13.3 MDS, HEL2, MDCR, KCIP-1, 14-3-3E -YWHAE and Endometrial Cancer
BCOR Xp11.4 MAA2, ANOP2, MCOPS2 -BCOR and Endometrial Cancer
PPP2R1A 19q13.41 MRD36, PP2AA, PR65A, PP2AAALPHA, PP2A-Aalpha -PPP2R1A and Endometrial Cancer
HSD17B2 16q23.3 HSD17, SDR9C2, EDH17B2 -HSD17B2 and Endometrial Cancer
POLE 12q24.3 FILS, POLE1, CRCS12 -POLE and Endometrial Cancer
PIK3R1 5q13.1 p85, AGM7, GRB1, IMD36, p85-ALPHA -PIK3R1 and Endometrial Cancer
GPER1 7p22.3 mER, CEPR, GPER, DRY12, FEG-1, GPR30, LERGU, LyGPR, CMKRL2, LERGU2, GPCR-Br -GPER and Endometrial Cancer
ETV5 3q27.2 ERM -ETV5 and Endometrial Cancer
SFRP4 7p14.1 PYL, FRP-4, FRPHE, sFRP-4 -SFRP4 and Endometrial Cancer
PIK3CB 3q22.3 PI3K, PIK3C1, P110BETA, PI3KBETA -PIK3CB and Endometrial Cancer
POLD1 19q13.33 CDC2, MDPL, POLD, CRCS10 -POLD1 and Endometrial Cancer
HSD17B1 17q21.2 E2DH, HSD17, EDHB17, EDH17B2, SDR28C1, 17-beta-HSD, 20-alpha-HSD -HSD17B1 and Endometrial Cancer
RBL2 16q12.2 Rb2, P130 Prognostic
-RBL2 and Endometrial Cancer
PAPPA 9q33.1 PAPA, DIPLA1, PAPP-A, PAPPA1, ASBABP2, IGFBP-4ase -PAPPA and Endometrial Cancer
ADIPOR1 1q32.1 CGI45, PAQR1, ACDCR1, CGI-45, TESBP1A -ADIPOR1 and Endometrial Cancer
ESR2 14q23.2-q23.3 Erb, ESRB, ESTRB, NR3A2, ER-BETA, ESR-BETA -ESR2 and Endometrial Cancer
IGFBP1 7p12.3 AFBP, IBP1, PP12, IGF-BP25, hIGFBP-1 -IGFBP1 and Endometrial Cancer
PAEP 9q34.3 GD, GdA, GdF, GdS, PEP, PAEG, PP14 -PAEP and Endometrial Cancer
ADIPOR2 12p13.31 PAQR2, ACDCR2 -ADIPOR2 and Endometrial Cancer
BAG1 9p13.3 HAP, BAG-1, RAP46 Overexpression
-BAG1 overexpression in Endometrial Cancer
HTRA1 10q26.13 L56, HtrA, ARMD7, ORF480, PRSS11, CARASIL, CADASIL2 -HTRA1 and Endometrial Cancer
PIK3R2 19p13.11 p85, MPPH, P85B, MPPH1, p85-BETA -PIK3R2 and Endometrial Cancer
LEPR 1p31.3 OBR, OB-R, CD295, LEP-R, LEPRD -LEPR and Endometrial Cancer
ERRFI1 1p36.23 MIG6, RALT, MIG-6, GENE-33 -ERRFI1 and Endometrial Cancer
EBAG9 8q23.2 EB9, PDAF -EBAG9 and Endometrial Cancer
KLLN 10q23.31 CWS4, KILLIN -killin protein, human and Endometrial Cancer
NUTM2A 10q23.2 FAM22A -NUTM2A and Endometrial Cancer
TRIM27 6p22.1 RFP, RNF76 -TRIM27 and Endometrial Cancer
ARHGEF5 7q35 P60, TIM, GEF5, TIM1 -ARHGEF5 and Endometrial Cancer
ARID5B 10q21.2 MRF2, DESRT, MRF-2 -ARID5B mutations in Endometrial Carcinoma
CTNND1 11q12.1 CAS, p120, CTNND, P120CAS, P120CTN, p120(CAS), p120(CTN) -CTNND1 and Endometrial Cancer

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

Latest Publications

An HJ, Song DH
Displacement of Vitamin D Receptor Is Related to Lower Histological Grade of Endometrioid Carcinoma.
Anticancer Res. 2019; 39(8):4143-4147 [PubMed] Related Publications
BACKGROUND/AIM: Vitamin D analogs have a protective effect on carcinogenesis in humans. Since vitamin D receptor (VDR) is detected in many histotypes of cancer, this study evaluated the role of VDR expression in endometrioid carcinoma.
MATERIALS AND METHODS: Tumor samples were collected from 60 patients who had undergone surgery, and the pattern of VDR expression assessed in tissue microarray (TMA) blocks of tumor samples. When VDR expression in the cytoplasm was higher than that in the nucleus, this was noted as 'displacement'. Using statistical analysis, the relationship between VDR expression and clinicopathological factors was evaluated.
RESULTS: Immunohistochemical staining of nuclear VDR was as follows: Negative: 32 (53.3%); mild: 13 (21.7%); moderate: 14 (23.3%); strong: 1 (1.7%). For cytoplasmic VDR expression: Negative: 2 (3.3%); mild: 19 (31.7%); moderate: 31 (51.7%); strong: 7 (11.7%). VDR displacement was found in 42 (70%) cores. VDR displacement was significantly positively correlated with endometrioid carcinoma having lower histological grade (1, p=0.03).
CONCLUSION: Displacement of VDR was significantly correlated with lower histological grade. Clinicians might be able to predict prognosis and decide therapies related to vitamin D analogs using this remarkable biomarker for endometrial carcinoma.

Penolazzi L, Bonaccorsi G, Gafà R, et al.
SLUG/HIF1-α/miR-221 regulatory circuit in endometrial cancer.
Gene. 2019; 711:143938 [PubMed] Related Publications
BACKGROUND AND PURPOSE: The pathogenesis of endometrial cancer (EC) involves many regulatory pathways including transcriptional regulatory networks supported by transcription factors and microRNAs only in part known. The aim of this retrospective study was to explore the possible correlation in the EC microenvironment between master regulators of complex phenomena such as steroid responsiveness through estrogen receptor alpha (ERα) and progesterone receptor (PR), epithelial-to-mesenchymal transition (supported by SLUG transcription factor), hypoxia (with hypoxia inducible factor-1 alpha, HIF-1α), and obesity that has been recognized as a EC risk factor.
METHODS: Formalin-Fixed Paraffin-Embedded (FFPE) blocks from University of Ferrara Pathology Archive were used and allocated into 2 groups according to their immunohistochemical positivity to ERα and PR, distinguishing the samples with a more benign prognosis (ERα
RESULTS: We showed a comparable percentage of HIF1-α and SLUG positive samples in the ERα
CONCLUSIONS: A molecular circuit of mutual regulation between ERα, PR, HIF1-α, SLUG and miR-221 is feasible in the EC and was firstly suggested by our research. In this interplay miR-221 seems to be in a nodal point of the regulatory system that is particularly strengthened by the metabolic changes in obesity.

Wasniewski T, Kiezun J, Krazinski BE, et al.
WNT5A gene and protein expression in endometrial cancer.
Folia Histochem Cytobiol. 2019; 57(2):84-93 [PubMed] Related Publications
INTRODUCTION: WNT5A (Wnt family member 5A) belongs to the WNT family of secreted signaling glycoproteins that play essential role in developmental, physiological and pathological processes. WNT5A was shown to take part in carcinogenesis process playing both oncogenic and suppressor functions in various types of human malignancies. This study aimed to assess the expression of the WNT5A gene at the mRNA and protein levels in the specimens derived from endometrial cancer (EC) or unchanged control endometrium. The associations between the WNT5A expression levels and clinicopathological characteristics and survival of EC patients were evaluated.
MATERIALS AND METHODS: Total RNA was isolated in order to assess the relative amounts of WNT5A mRNA by quantitative polymerase chain reaction (QPCR) in samples of unchanged endometrial control (n = 8) and tumor samples of EC patients (n = 28). Immunohistochemistry (IHC) was used to determine the presence of WNT5A protein in the sections of formalin-fixed, paraffin-embedded tissue specimens derived from unchanged endome-trial controls (n = 6) and EC tumors (n = 19). Significance of differences in WNT5A expression levels between the studied groups of EC patients and correlations between the WNT5A and demographic data, pathological features, hematological parameters and overall survival of the patients were evaluated by statistical analysis.
RESULTS: The level of WNT5A mRNA was decreased in EC in comparison to unchanged endometrium. WNT5A expression was associated with primary tumor invasion status exhibiting reduced level of transcripts in EC that involved organs beyond the uterus when compared to the uterus-confined cancers. WNT5A immunoreactivity was visualized in the cytoplasm and nuclei of EC cells as well as in the luminal and glandular epithelial cells of unchanged endometrium. WNT5A mRNA expression levels correlated negatively with cytoplasmic, and positively with nuclear immunoreactivity of the WNT5A protein in the EC cells. In addition, the relationships between blood leucocyte count (in particular granulocytes and lymphocytes) of patients with EC and their WNT5A mRNA and protein expression levels were established. A positive correlation between the nuclear immunoexpression of WNT5A protein in the cancer cells in cell nuclei and mean platelet volume in blood was also found.
CONCLUSIONS: The results of the first study of WNT5A expression at the transcript and protein levels indicate that it could be considered as a potential marker of molecular changes that take place during EC development.

Reijnen C, Küsters-Vandevelde HVN, Prinsen CF, et al.
Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer.
Gynecol Oncol. 2019; 154(1):124-130 [PubMed] Related Publications
BACKGROUND: Mismatch repair (MMR) deficiency is found in 20 to 40% of endometrial cancers (ECs) and was recently identified as a discerning feature of one of the four prognostic subgroups identified by The Cancer Genome Atlas. There is accumulating evidence that MMR proteins are involved in the DNA repair processes following radiotherapy. We investigated the predictive value of MMR status for response to adjuvant radiotherapy in patients with stage IB/II, grade 3 endometrioid endometrial cancer (EEC).
METHODS: A retrospective multicenter cohort study was performed to compare patients with histopathologically confirmed stage IB/II grade 3 EEC with and without adjuvant radiotherapy. Patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifying ECs as either MMR-deficient, POLE, p53abn or p53wt. Multivariable Cox regression analysis explored associations between adjuvant treatment and outcome.
RESULTS: A total of 128 patients were analyzed, including 57 patients (43.0%) with MMR-deficient EECs. Baseline characteristics were comparable, except a higher proportion of MMR-deficient EECs were stage II (36.8% vs. 15.5%, p = 0.006). Eighty-two patients (64.1%) received adjuvant radiotherapy (external beam [n = 55], vaginal brachytherapy [n = 27]). In multivariable analysis, adjuvant radiotherapy was associated with improved disease-specific survival in patients with MMR-deficient EECs (hazard ratio 0.19, 95%-CI 0.05-0.77), but not in patients with MMR-proficient EECs (hazard ratio 0.92, 95%-CI 0.37-2.31).
CONCLUSION: Adjuvant radiotherapy improved survival in patients with MMR-deficient EECs. MMR status could be used as a predictive biomarker to select patients that benefit most from adjuvant radiotherapy.

Wujcicka W, Zając A, Stachowiak G
Impact of
In Vivo. 2019 May-Jun; 33(3):917-924 [PubMed] Free Access to Full Article Related Publications
BACKGROUND/AIM: The aim of this study was to determine the joint effect of single nucleotide polymorphisms (SNPs) of MDM2, TP53, and CDKN2A (P14ARF) genes on the onset and course of endometrial cancer (EC) in postmenopausal women.
MATERIALS AND METHODS: The study group consisted of 144 EC women and 50 non-cancer controls. MDM2 rs22279744, TP53 rs1042522, and P14ARF rs3088440, rs3731217, and rs3731245 SNPs were analysed.
RESULTS: The double-SNP combinations T-C, T-T, or T-G in MDM2 SNP 309 and P14ARF polymorphisms decreased EC risk. The triple-SNP combinations T-C-T, T-C-G, or T-T-G in MDM2 SNP and two P14ARF polymorphisms decreased EC risk. The multiple-SNP combination T-C-T-G in MDM2 and three P14ARF polymorphisms decreased EC risk. The G-Arg-C-T-G carriers were at increased EC risk, while the T-Arg-C-T-G carriers were at decreased EC risk.
CONCLUSION: MDM2 SNP309 plays a role in EC onset in postmenopausal women.

Zhou M, Liu C, Cao G, et al.
Expression of polymeric immunoglobulin receptor and its biological function in endometrial adenocarcinoma.
J Cancer Res Ther. 2019; 15(2):420-425 [PubMed] Related Publications
Aim: To investigate the expression of polymeric immunoglobulin receptor (pIgR) in endometrial adenocarcinoma and the relationship between pIgR and the clinicopathological features of endometrial adenocarcinoma. To investigate the role of pIgR in the biological behavior of endometrial adenocarcinoma cell lines.
Methods: First, the paraffin-embedded endometrial adenocarcinoma samples and clinicopathological data from the Chao-Yang Hospital were collected. Next, immunohistochemistry was conducted to test the expression of pIgR in endometrial adenocarcinoma; the correlations between pIgR and clinicopathological features were detected. Then, the expression of pIgR in the Ishikawa cells was interfered with short-interfering RNA (siRNA). Finally, the migration and proliferation abilities of Ishikawa cells were detected by transwell and CCK8 assays before and after interference.
Results: pIgR had a high expression level and higher H-score in endometrial adenocarcinoma (P = 0.013) than in noncancerous tissues. There was no correlation between pIgR and the histopathological features of endometrial adenocarcinoma (P ≥ 0.418). The migration ability of Ishikawa cells was increased after interference with pIgR (P = 0.023). The proliferation of Ishikawa cells was not different between the untreated and siRNA215-treated groups (P = 0.967).
Conclusion: PIgR may be a predictive biomarker of endometrial adenocarcinoma and a potential target protein for immunotherapy of endometrial adenocarcinoma.

Wang X, Sun X, Mu L, Chen W
Cancer-Associated Fibroblasts Induce Epithelial-Mesenchymal Transition in Endometrial Cancer Cells by Regulating Pituitary Tumor Transforming Gene.
Cancer Invest. 2019; 37(3):134-143 [PubMed] Related Publications
Cancer-associated fibroblasts (CAFs) play an important role in the development and progression of cancer by inducing epithelial-mesenchymal transition (EMT). In this study, we investigated the role of CAFs in endometrial cancer (EC) cells. We found that the pituitary tumor transforming gene (PTTG) expression was significantly increased in EC cell lines compared to normal human endometrial epithelial cells. Furthermore, CAFs could induce PTTG over-expression and increase EC cell invasion and migration in vitro. In addition, CAFs also induced EMT in EC cells. This study demonstrated that CAFs induced EMT in endometrial cancer cells by regulating PTTG.

Veneris JT, Lee EK, Goebel EA, et al.
Diagnosis and management of a recurrent polymerase-epsilon (POLE)-mutated endometrial cancer.
Gynecol Oncol. 2019; 153(3):471-478 [PubMed] Related Publications
Polymerase-epsilon (POLE)-mutated carcinomas are a rare, but well-known subtype of endometrial cancer. While typically associated with good prognosis, recurrences are documented. Here we present a case of recurrent POLE-mutated endometrial cancer, discuss pathologic features, current methods of molecular classification, and explore therapeutic implications for the POLE-mutation phenotype.

Zhou JW, Tang JJ, Sun W, Wang H
PGK1 facilities cisplatin chemoresistance by triggering HSP90/ERK pathway mediated DNA repair and methylation in endometrial endometrioid adenocarcinoma.
Mol Med. 2019; 25(1):11 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Endometrial carcinoma represents one of the most common cancer types of the female reproductive tract. If diagnosed at an early stage, the 5-year survival rate is promising. However, recurrence and chemoresistance remain problematic for at least 15% of the patients. In the present study, we aim to reveal the mechanism by which PGK1 regulates chemoresistance in endometrial carcinoma.
METHODS: qPCR was performed to detect expression of PGK1 in clinical tissue samples of endometrial carcinoma. Specific shRNAs were employed to knockdown PGK1 expression in endometrial cancer cell lines. MTT assay was used to evaluate cell viability and cisplatin sensitivity of endometrial carcinoma cell lines. Western blot was performed to assess the effects of PGK1 knockdown on the expression levels of HSP90, DNA repair-associated proteins (c-JUN, FOSL1, and POLD1), and DNA methylation-related enzymes (DNMT1, DNMT3A and DNMT3B). Immunoprecipitation was performed to verify direct binding between PGK1 and HSP90.
RESULTS: We first showed that PGK1 expression is elevated in tumor tissues of endometrial cancer, and high PGK1 levels are associated with clinical stages and metastasis. Knockdown of PGK1 inhibits proliferation of endometrial cancer cells, and enhances the inhibitory effect of cisplatin on cell viability. In addition, knockdown of PGK1 down-regulates the expression of DNA repair-related proteins, methylation-related enzymes, and total cellular methylation level. PGK1 was next shown to interact directly with HSP90 and exhibit pro-tumor effects by modulating the ATPase activity of HSP90.
CONCLUSIONS: We propose that PGK1 mediates DNA repair and methylation through the HSP90/ERK pathway, and eventually enhances the chemoresistance to cisplatin. The results provide new insights on functions of PGK1 and HSP90, which might make them as promising targets for endometrial cancer chemotherapy.

Moroney MR, Davies KD, Wilberger AC, et al.
Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers.
Gynecol Oncol. 2019; 153(3):517-520 [PubMed] Related Publications
OBJECTIVES: Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence.
METHODS: A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing.
RESULTS: 15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, p = 0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, p = 0.03). POLE mutations were found in 0% of cases vs. 7% of controls (p = 0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (p < 0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (p < 0.001).
CONCLUSIONS: Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population.

Wu J, Zhang W, Cai J, et al.
Influence of IL-1R2 polymorphisms on endometrial cancer susceptibility in the Chinese Han population.
Mol Genet Genomic Med. 2019; 7(5):e650 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Recently, many studies have identified that genetic factor plays a crucial role in endometrial cancer development. The purpose of this study is to investigate the influence of single nucleotide polymorphisms (SNPs) of IL-1R2 on endometrial cancer susceptibility.
METHODS: We performed a case-control study that included 293 patients with endometrial cancer and 579 healthy controls. Six SNPs in the IL-1R2 gene were genotyped using the Agena MassARRAY platform. Genetic models and haplotype analyses were used to assess the association between SNPs and endometrial cancer risk by computing odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: Overall analysis results found that two SNPs (rs4851527 and rs3218896) and haplotypes TGTC and TACT were significantly associated with endometrial cancer risk. Stratified analysis by age showed that rs2072472 was associated with endometrial cancer risk in age >54 subgroup.
CONCLUSIONS: These findings suggested that IL-1R2 polymorphisms may contribute to the development of endometrial cancer. Further studies are required to confirm the results.

Miller MD, Devor EJ, Salinas EA, et al.
Population Substructure Has Implications in Validating Next-Generation Cancer Genomics Studies with TCGA.
Int J Mol Sci. 2019; 20(5) [PubMed] Free Access to Full Article Related Publications
In the era of large genetic and genomic datasets, it has become crucially important to validate results of individual studies using data from publicly available sources, such as The Cancer Genome Atlas (TCGA). However, how generalizable are results from either an independent or a large public dataset to the remainder of the population? The study presented here aims to answer that question. Utilizing next generation sequencing data from endometrial and ovarian cancer patients from both the University of Iowa and TCGA, genomic admixture of each population was analyzed using STRUCTURE and ADMIXTURE software. In our independent data set, one subpopulation was identified, whereas in TCGA 4⁻6 subpopulations were identified. Data presented here demonstrate how different the genetic substructures of the TCGA and University of Iowa populations are. Validation of genomic studies between two different population samples must be aware of, account for and be corrected for background genetic substructure.

Cai J, Cui K, Niu F, et al.
Genetics of IL6 polymorphisms: Case-control study of the risk of endometrial cancer.
Mol Genet Genomic Med. 2019; 7(4):e00600 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Endometrial cancer is the most common gynaecological malignancy. Cytokines gene may be important in endometrial cancer development. This study sought to investigate whether the IL4, IL6 two gene genetic variants were associated with susceptibility to endometrial cancer (EC) in Hainan Chinese Han women by a hospital-based study.
METHODS: The genetic polymorphisms for IL4 and IL6 were analyzed by Agena MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression.
RESULTS: We observed a significant increase in risk of endometrial cancer of rs1524107 (IL6) (T/C, OR = 1.61, 95% CI = 1.09-2.37, p = 1.55 × 10
CONCLUSION: This study demonstrated that IL6 gene polymorphisms are significantly associated with increased EC susceptibility in Hainan Chinese Han women.

Brooks RA, Tritchler DS, Darcy KM, et al.
GOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study.
Gynecol Oncol. 2019; 153(2):335-342 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: The ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients.
METHODS: Surgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated.
RESULTS: 361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables.
CONCLUSION: SNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.

Wu YS, Lin H, Chen D, et al.
A four-miRNA signature as a novel biomarker for predicting survival in endometrial cancer.
Gene. 2019; 697:86-93 [PubMed] Related Publications
BACKGROUND: The microRNAs (miRNAs) have been validated as prognostic markers in many cancers. The aim of this study was to identify new miRNA prognostic biomarkers in endometrial cancer (EC) and to develop an expression-based miRNA signature to provide survival risk prediction for EC patients.
METHODS: From TCGA database, the miRNA datasets of EC and clinical information were downloaded in April 2018. Using univariate and multivariate Cox regression analyses identify prognostic factors. Using area under the curve (AUC) of receiver operating characteristic (ROC) curve assess the sensitivity and specificity of prognostic model.
RESULTS: 530 patients were randomly divided into training set and testing set. Among 561 differentially expressed miRNAs, 4 miRNAs (miR-4758, miR-876, miR-142, miR-190b) were demonstrated to be predictive biomarkers of overall survival (OS) for EC patients in training set. Based on the risk score of 4-miRNA model, patients in the training set were divided into high-risk and low-risk groups with significantly different OS. This 4-miRNA model was validated in testing and entire set. The AUC for the ROC curves in the entire set was 0.704. Meanwhile, multivariate Cox regression combined with other traditional clinical parameters indicated that the 4-miRNA model can be used as an independent OS prognostic factor. Functional enrichment analysis revealed that these miRNAs are involved in biological processes and pathways that are closely related to cancer.
CONCLUSION: A robust 4-miRNA signature as an independent prognostic factor for OS in EC patients was established.

Tan A, Luo R, Ruan P
miR-495 promotes apoptosis and inhibits proliferation in endometrial cells via targeting PIK3R1.
Pathol Res Pract. 2019; 215(3):594-599 [PubMed] Related Publications
Endometrial cancer (EC) is a huge threat to women's health. The aims of this study were to investigate the role of microRNA (miR)-495 in the proliferation and apoptosis of EC cells in vitro. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA levels. In addition, dual-luciferase reporter assay was used to verified that PIK3R1 was a target of miR-495. After transfection with miR-495 mimics, Cell Counting Kit 8 (CCK-8) assay was performed to evaluate the cell viability of EC cells. The protein expression of PIK3R1, vascular endothelial growth factor (VEGF), Bcl-2, Bax, caspase 3 after transfection was analyzed using western blotting. Furthermore, cell apoptosis rate of EC cells was evaluated by flow cytometry. These results showed that miR-495 was significantly down-regulated in tumor tissues compared with the adjacent normal tissues, while PIK3R1 was up-regulated. The proliferation of the EC cells that were transfected with miR-495 mimics was markedly inhibited, and apoptosis was significantly promoted. In addition, downregulated expression of PIK3R1, Bcl-2, VEGF expression and upregulated expression of Bax and caspase 3 expression were observed after transfected with miR-495 mimic. Together these findings indicated that miR-495 acts as a tumor suppressor gene by directly targeting PIK3R1 at the post-transcriptional level in EC cells in vitro.

McDonald ME, Bender DP
Endometrial Cancer: Obesity, Genetics, and Targeted Agents.
Obstet Gynecol Clin North Am. 2019; 46(1):89-105 [PubMed] Related Publications
It is imperative to understand the underlying mechanisms of both endometrial carcinogenesis and recurrence in order to develop more effective prevention and treatment. This article reviews available molecular data, the interplay between endometrial cancer carcinogenesis with obesity and genetics, as well as current targeted therapies.

Li L, Shou H, Wang Q, Liu S
Investigation of the potential theranostic role of KDM5B/miR-29c signaling axis in paclitaxel resistant endometrial carcinoma.
Gene. 2019; 694:76-82 [PubMed] Related Publications
OBJECTIVE: Endometrial cancer (EC) is one of the most common female reproductive system tumors. In this study, we explored the clinical significance of Histone demethylase KDM5B gene and its effects on paclitaxel (PTX) sensitivity in EC.
METHOD: First, we found that KDM5B expression significantly higher in EC tissues and cell lines. The elevated KDM5B expression was associated with high pathological grade and low PTX sensitivity. The functional role of KDM5B in PTX-resistant Ishikawa-R and HEC1A-R cells were examined by gene silencing experiments.
RESULTS: Knockdown of KDM5B resulted in the re-sensitization towards paclitaxel in both resistant cell lines. In addition, we also identified that microRNA-29c-3p (a tumor suppressor) was significantly lower in the EC cells and linked to the low PTX sensitivity of EC. The up-regulation of miR-29c-3p using exogenous mimic molecules markedly increased PTX sensitivity in both cell lines and reduced expression of KDM5B while the inhibitor of miR-29-3p resulted in the opposite effects. Notably, we also demonstrated that the level of miR-29c-3p was inversely correlated to the invasive, colony-forming abilities and PTX resistance in both cell lines. We also identified that miR-29c-3p has a binding site in the 3'UTR of the KDM5B gene, establishing a link of this signaling axis. In conclusion, high-expression of KDM5B is associated with the poor response to PTX in EC patients. Silencing of KDM5B led to the reversal of PTX resistance through miR-29c-3p/KDM5B pathway in EC.
CONCLUSION: Our findings provide new insights into the mechanism by which EC cells acquire paclitaxel resistance and potential this signaling as a theronostic marker for this malignancy.

Monsivais D, Peng J, Kang Y, Matzuk MM
Activin-like kinase 5 (ALK5) inactivation in the mouse uterus results in metastatic endometrial carcinoma.
Proc Natl Acad Sci U S A. 2019; 116(9):3883-3892 [PubMed] Free Access to Full Article Related Publications
The endometrial lining of the uterine cavity is a highly dynamic tissue that is under the continuous control of the ovarian steroid hormones, estrogen and progesterone. Endometrial adenocarcinoma arises from the uncontrolled growth of the endometrial glands, which is typically associated with unopposed estrogen action and frequently occurs in older postmenopausal women. The incidence of endometrial cancer among younger women has been rising due to increasing rates of obesity, a major risk factor for the disease. The transforming growth factor β (TGFβ) family is a highly conserved group of proteins with roles in cellular differentiation, proliferation, and cancer. Inactivating mutations in the genes encoding the TGFβ cell surface receptors (

Meng X, Yang S, Li Y, et al.
Combination of Proteasome and Histone Deacetylase Inhibitors Overcomes the Impact of Gain-of-Function p53 Mutations.
Dis Markers. 2018; 2018:3810108 [PubMed] Free Access to Full Article Related Publications
Mutations in the "guardian of the genome"

Ozgor BY, Iyibozkurt C, Bastu E, et al.
Investigation of resistin 420 and 62 gene polymorphism in patients with endometrial cancer.
Taiwan J Obstet Gynecol. 2019; 58(1):164-167 [PubMed] Related Publications
OBJECTIVE: We aimed to assess resistin gene polymorphisms, namely 420C > G and 62G > A and their effect on the risk of endometrial cancer (EC).
MATERIALS AND METHODS: Between January 2012 and January 2015, of the total of 183 patients diagnosed with EC, 94 patients were enrolled into the study. Patients with diabetes mellitus, hypertension and history of any other cancer were excluded. To identify the importance of nucleotide polymorphism including 420C > G and 62G > A in the resistin gene, 94 healthy volunteers were included as the control group.
RESULTS: Among the Resistin 420 gene polymorphism profiles, 420 GC (47.9%) was the most common gene polymorphism in the EC group. Also, the polymorphism of 420 CC (57.7%, p: 0.002) lead the list in the control group followed by the 420GC (37.5%) polymorphism. Resistin 62 gene polymorphism analysis demonstrated that the 62GC polymorphism was significantly more common in the EC group (p < 0.01), while 62 AG (52.9%) was observed most frequently in the control group bringing about a reduction in the risk of EC (p < 0.01, Odds Ratio:0.37). Additionally, the alleles of 420G+ and 62A + were significantly more common in the EC group and the control group, respectively (p:0.02 and p<:0.01). Multivariate regression analysis revealed that the presence of 420G + allele increased the EC risk 1.99 fold while the presence of 62A + allele was shown to decrease the risk of EC (p<:0.01 Odds Ratio:0.038).
CONCLUSION: Our study for the first time had demonstrated that Resistin 420G > C and 62G > A gene polymorphisms play a role in EC development.

Shu S, Liu X, Xu M, et al.
MicroRNA-320a acts as a tumor suppressor in endometrial carcinoma by targeting IGF-1R.
Int J Mol Med. 2019; 43(3):1505-1512 [PubMed] Related Publications
Dysregulation of microRNAs (miRs) is implicated in the carcinogenesis of various types of malignant tumor by manipulating cell growth and apoptosis. Abnormal expression of miR‑320a is involved in tumorigenesis of many types of cancer. The potential association of miR‑320a and the possible regulatory mechanisms in endometrial carcinoma is rarely elucidated. In the present study, it was demonstrated that miR‑320a expression was decreased in endometrial carcinoma tissues and cell lines. The present results also indicated that overexpression of miR‑320a suppressed cell proliferation through inducing G2/M phrase arrest and apoptosis. Insulin‑like growth factor receptror‑1 (IGF‑1R) was verified to be the potential target of miR‑320a by computational analysis and luciferase reporter assays. In addition, overexpression of miR‑320a reduced endogenous IGF‑1R expression in cells. Furthermore, it was demonstrated that upregulation of miR‑320a inhibited phosphorylated (p)‑protein kinase B and p‑mechanistic target of rapamycin activation and promoted B cell lymphoma‑2‑associated death promoter expression. Reintroduction of IGF‑1R into miR‑320a‑overexpressed cells antagonized the impact of miR‑320a on its downstream protein, which demonstrated that the tumor suppressive role of miR‑320a in endometrial carcinoma is exerted by the signal pathway mediated by IGF‑1R. It was therefore concluded that miR‑320a served an anti‑tumor role on endometrial carcinoma through the regulation of IGF‑1R, and miR‑320a may be used as the target for the gene therapy of endometrial carcinoma.

Long B, Lilyquist J, Weaver A, et al.
Cancer susceptibility gene mutations in type I and II endometrial cancer.
Gynecol Oncol. 2019; 152(1):20-25 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
OBJECTIVES: To determine the incidence of germline cancer predisposition gene mutations in patients with endometrial cancer (EC) subtypes.
METHODS: Germline DNA was extracted from whole blood collected from consenting patients undergoing primary surgery for EC between 5/2005 and 11/2016. DNA samples were evaluated by product sequencing from a targeted multiplex PCR panel including 21 known/suspected cancer predisposition genes. Variants were classified as pathogenic/likely pathogenic based on allele frequency (<0.003), effects on protein function, and ClinVar assertions.
RESULTS: Germline panel testing was performed on 1170 cases of EC; 849 (72.6%) were type I, and 321 (27.4%) were type II EC, including 135 (11.5%) uterine serous cancers (USC). BRCA1 mutations were enriched in Type II EC compared to Type I EC (0.93% vs. 0.12%, p = 0.07). Lynch Syndrome (LS) mutations were identified in 1.4% of type I and 1.6% of type II EC (p = 0.79), including 1.5% for USC. In total, predisposition gene mutations were present in 4.2% of type I and 5.3% of type II EC, as well as 6.7% of patients with USC).
CONCLUSIONS: BRCA1/2 and Lynch mutations were rare in this cohort of unselected patients with type I and II EC, including USC. However, the presence of predisposition gene mutations in 4.2% of EC type I, 5.3% of EC type II, and 6.7% of USC suggests that somatic mutation testing should be considered for all EC patients.

Zheng X, Liu M, Song Y, Feng C
Long Noncoding RNA-ATB Impairs the Function of Tumor Suppressor miR-126-Mediated Signals in Endometrial Cancer for Tumor Growth and Metastasis.
Cancer Biother Radiopharm. 2019; 34(1):47-55 [PubMed] Related Publications
OBJECTIVE: Long non-coding RNA-ATB (Lnc-ATB) have been reported to promote tumor proliferation and metastasis via regulation of tumor suppressive miRNA-related signals. Patients with endometrial cancer (EC) have advanced stage disease or metastasis have poor prognosis. We here investigated the role of Lnc-ATB in endometrial cancer.
METHODS: Endometrial cancer tissues and normal tissues (n = 35) were collected to determine the expression and clinical significance of Lnc-ATB, and bioinformatics analysis was used to predict the miRNA target. siRNA was used to estimate the function of Lnc-ATB in EC cell lines and in vivo.
RESULT: The expression of Lnc-ATB is up-regulated in tumor tissues and EC cell lines. Patients with high expressed Lnc-ATB have high FIGO stage and poor tumor differentiation. The tumor suppressor miR-126 interacted with Lnc-ATB. Down-regulated miR-126 negative correlated with FIGO stage and tumor differentiation. Knockdown of Lnc-ATB in RL95 and HEC1A cell lines increased the miR-126 level and impaired the cell vitality, induced caspase-3-related tumor apoptosis and G1/S arrest. However, abrogation of miR-126 by its inhibitors counteracted Lnc-ATB knockdown-induced tumor inhibition via regulation of miR-126 target gene PIK3R2 and Sox2-related apoptosis and cell cycle pathway. Meanwhile, Lnc-ATB knockdown also suppressed the migration and invasion and inhibited TGF-β-induced epithelial-mesenchymal transition (EMT) phenotype via miR-126. Knockdown of Lnc-ATB in vivo remarkably induced tumor regression via restoration of tumor suppressor miR-126, leading to deceased tumor volume, reduced expression of PCNA and PIK3R2/Sox2 signals and EMT phenotype in tumor tissues.
CONCLUSION: These data demonstrate the tumorigenic role of Lnc-ATBs in endometrial cancer via abrogation of tumor suppressor miR-126 signals.

Wakinoue S, Chano T, Amano T, et al.
ADP-ribosylation factor-like 4C predicts worse prognosis in endometriosis-associated ovarian cancers.
Cancer Biomark. 2019; 24(2):223-229 [PubMed] Related Publications
BACKGROUND: Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are both classified as endometriosis-associated ovarian cancer (EAOC). Despite the high rates of recurrence and mortality of EAOC, no prognostic biomarkers have been determined. ADP-ribosylation factor-like protein 4C (ARL4C) has been reported to be involved in various tumor progression processes, but its clinical significance for predicting prognosis in EAOC cases has never been studied.
OBJECTIVE: The present study aimed to determine the clinical significance of ARL4C expression in EAOC prognosis.
METHODS: ARL4C expression was semi-quantitatively evaluated via immunohistochemistry in 61 EAOC patients, and the correlations between ARL4C expression and clinicopathological data and survival were statistically analyzed.
RESULTS: Thirty-six (59%) cases had high levels of ARL4C, which was related to worse 5-year overall survival (OS) (log-rank test, p= 0.036). In multivariate Cox proportional hazard model, high ARL4C expression was a significantly independent predictive factor for worse 5-year OS (hazard ratio = 12.048, p= 0.0201) and 5-year PFS (hazard ratio = 8.130, p= 0.0036).
CONCLUSIONS: ARL4C is a biomarker for worse prognosis and a novel therapeutic target in EAOC.

Lu H, Ju DD, Yang GD, et al.
Targeting cancer stem cell signature gene SMOC-2 Overcomes chemoresistance and inhibits cell proliferation of endometrial carcinoma.
EBioMedicine. 2019; 40:276-289 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
BACKGROUND: Endometrial cancer is one of the most common gynecological malignancies and has exhibited an increasing incidence rate in recent years. Cancer stem cells (CSCs), which are responsible for tumor growth and chemoresistance, have been confirmed in endometrial cancer. However, it is still challenging to identify endometrial cancer stem cells to then target for therapy.
METHODS: Flow cytometry was used to identify the endometrial cancer stem cells. Sphere formation assay, western blotting, qRT-PCR assay, cell viability assay, xenograft assay and immunohistochemistry staining analysis were utilized to evaluate the effect of SPARC-related modular calcium binding 2 (SMOC-2) on the cells proliferation and drug resistance. Cell viability assay, qRT-PCR assay, immunofluorescence staining, Co-IP assay and luciferase reporter gene assay were performed to explore the possible molecular mechanism by which SMOC-2 activates WNT/β-catenin pathway.
FINDINGS: We found the expression of SPARC-related modular calcium binding 2 (SMOC-2), a member of SPARC family, was higher in endometrial CSCs than that in non-CSCs. SMOC-2 was also more highly expressed in spheres than in monolayer cultures. The silencing of SMOC-2 suppressed cell sphere ability; reduced the expression of the stemness-associated genes SOX2, OCT4 and NANOG; and enhanced chemosensitivity in endometrial cancer cells. By co-culture IP assay, we demonstrated that SMOC-2 directly interacted with WNT receptors (Fzd6 and LRP6), enhanced ligand-receptor interaction with canonical WNT ligands (Wnt3a and Wnt10b), and finally, activated the WNT/β-catenin pathway in endometrial cancer. SMOC-2 expression was closely correlated with CSC markers CD133 and CD44 expression in endometrial cancer tissue.
INTERPRETATION: Taken together, we conclude that SMOC-2 might be a novel endometrial cancer stem cell signature gene and therapeutic target for endometrial cancer. FUND: National Natural Science Foundation of China, Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission, Scientific and Technological Innovation Act Program of Fengxian Science and Technology Commission, Natural Science Foundation of Shanghai.

Klat J, Mladenka A, Dvorackova J, et al.
L1CAM as a Negative Prognostic Factor in Endometrioid Endometrial Adenocarcinoma FIGO Stage IA-IB.
Anticancer Res. 2019; 39(1):421-424 [PubMed] Related Publications
AIMS: In this study, we aimed to investigate how positivity for L1 cell adhesion molecule (L1CAM) was associated with outcome and relapse pattern in patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IA-IB endometrial cancer.
MATERIALS AND METHODS: This retrospective study included 358 patients who underwent surgical treatment for endometrial carcinoma. Tumor samples from 312 patients (87.2%) were available for L1CAM analysis by immunohistochemistry.
RESULTS: Of the 312 tumor samples analyzed, 93 (29.8%) were L1CAM-positive. L1CAM positivity was significantly more common in grade 3 compared to grade 1-2 carcinomas (p=0.02). Patients with L1CAM positivity more commonly experienced disease progression. Distant metastasis was significantly associated with L1CAM positivity (p=0.01). Progression-free interval and overall survival did not significantly differ between L1CAM-positive and L1CAM-negative cases.
CONCLUSION: L1CAM is a promising independent prognostic marker associated with aggressive tumor behavior and recurrence risk, but not with overall survival.

Su Y, Wang J, Ma Z, et al.
miR-142 Suppresses Endometrial Cancer Proliferation In Vitro and In Vivo by Targeting Cyclin D1.
DNA Cell Biol. 2019; 38(2):144-150 [PubMed] Related Publications
Endometrial cancer (EC), a prevalent gynecologic tumor, is a great threat to women. We aimed to explore miR-142's effects on EC and the relevant mechanisms. Cell proliferation was evaluated with MTT, cell counting, and colony formation assay. MRNA abundances of miR-142 and cyclin D1 (CCND1) were examined with quantitative real-time PCR. CCND1 protein level in cells was analyzed with Western blot. miR-142's downstream target was identified with targetscan and luciferase reporter assay. Nude mice were injected subcutaneously with Ishikawa (ISK) cells transfected with or without miR-142 mimics. Ki-67 and CCND1 expressions in tumors of xenograft mice were analyzed with immunohistochemical assay. miR-142 was expressed at a lower level in human EC tumor samples than matched normal tissues, and its mRNA level in EC patients without metastasis was higher than that in patients with metastatic EC. Additionally, low-level miR-142 was closely linked with the poor prognosis of EC patients. miR-142 restricted ISK and HEC-1A cell proliferation. Targetscan and luciferase reporter assay proved the target relationship between miR-142 and CCND1. Moreover, high-level CCND1 was positively correlated with the poor prognosis of EC patients. Besides, miR-142 mimics restricted tumor growth in ISK xenografted mice, as well as inhibited the expression of Ki67 and CCND1 in excised tumors. miR-142 restricted EC proliferation by targeting CCND1.

Jin W, Wang LQ, Liu Y, Liu AJ
[Expression and clinical significance of MMR protein and MLH1 promoter methylation testing in endometrial cancer].
Zhonghua Fu Chan Ke Za Zhi. 2018; 53(12):823-830 [PubMed] Related Publications

Malentacchi F, Turrini I, Sorbi F, et al.
Pilot investigation of the mutation profile of PIK3CA/PTEN genes (PI3K pathway) in grade 3 endometrial cancer.
Oncol Rep. 2019; 41(3):1560-1574 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Endometrial cancer (EC) comprises a biological and clinical heterogeneous group of tumors. Several genetic alterations are involved in the development and progression of EC, and may be used for targeted therapy, particularly in patients with advanced‑stage EC. In the present study, a combined procedure was developed based on polymerase chain reaction (PCR)‑high resolution melting analysis (HRMA) and Sanger sequencing for the evaluation of somatic mutations in selected phosphoinositide 3‑kinase (PI3K) catalytic subunit α (PIK3CA; exons 1, 9 and 21) and phosphatase and tensin homolog (PTEN; exons 5, 6, 7 and 8) exons. This combined procedure has the specificity and sensitivity of the two techniques, and overcomes their limitations. A pilot study was performed on 18 selected homogenous EC samples, of grade 3 endometrioid subtype (G3 EEC). First, the feasibility of the combined procedure was investigated to properly identify the presence of somatic mutations on PIK3CA and PTEN, the variations identified were analyzed using Catalogue of Somatic Mutations in Cancer, PolyPhen‑2 and Mutation Taster software, and the frequency of mutations/variations was determined in the selected samples. The evaluation of mutational load revealed that the majority of the G3 EEC samples exhibited PIK3CA mutations (39%) and PTEN mutations (67%), and the majority of the samples (83%) had mutations in at least one of the two genes, and 33% had mutations in the two genes. The results of the present pilot study suggested that the cost‑effective combined PCR‑HRMA and Sanger sequencing procedure may be suitable for identification of PTEN and PIK3CA mutations in G3 EEC and that their frequency was consistent in G3 EEC, indicating that the PI3K pathway serves a pivotal function that may have potential for defining targeted therapy for the treatment of G3 EEC.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. Endometrial Cancer, Cancer Genetics Web: http://www.cancer-genetics.org/X1005.htm Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 29 August, 2019     Cancer Genetics Web, Established 1999