Mutation frequencies in endometrial cancer patients of different ethnicities and tumor grades: An analytical study

Althubiti, Mohammad

doi:10.4103/sjmms.sjmms_154_18

Cited by 25 publications

(22 citation statements)

References 51 publications

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“…trajectory. PTEN alterations were less frequent in AFR patients and have also been reported to have a lower mutation frequency in AFR patients with endometrial cancer (24). A major limitation of the meta-analysis is that some cohorts lacked matched tumors from EUR men, limiting our ability to control for cohort-specific effects that could arise due to differences in region, clinical setting, or sequencing assay.…”

Section: Discussionmentioning

confidence: 99%

Genomic Profiling of Prostate Cancers from Men with African and European Ancestry

Koga

Song

Chalmers

et al. 2020

Clinical Cancer Research

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Purpose: African American (AFR) men have the highest mortality rate from prostate cancer (PCa) compared with men of other racial/ancestral groups. Differences in the spectrum of somatic genome alterations in tumors between AFR men and other populations have not been well-characterized due to a lack of inclusion of significant numbers in genomic studies. Experimental Design: To identify genomic alterations associated with race, we compared the frequencies of somatic alterations in PCa obtained from four publicly available datasets comprising 250 AFR and 611 European American (EUR) men and a targeted sequencing dataset from a commercial platform of 436 AFR and 3018 EUR men. Results: Mutations in ZFHX3 as well as focal deletions in ETV3 were more frequent in tumors from AFR men. TP53 mutations were associated with increasing Gleason score. MYC amplifications were more frequent in tumors from AFR men with metastatic PCa, whereas deletions in PTEN and rearrangements in TMPRSS2-ERG were less frequent in tumors from AFR men. KMT2D truncations and CCND1 amplifications were more frequent in primary PCa from AFR men. Genomic features that could impact clinical decision making were not significantly different between the two groups including tumor mutation burden, MSI status, and genomic alterations in select DNA repair genes, CDK12, and in AR. Conclusions: Although we identified some novel differences in AFR men compared with other populations, the frequencies of genomic alterations in current therapeutic targets for PCa were similar between AFR and EUR men, suggesting that existing precision medicine approaches could be equally beneficial if applied equitably.

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Section: Discussionmentioning

confidence: 99%

Genomic Profiling of Prostate Cancers from Men with African and European Ancestry

Koga

Song

Chalmers

et al. 2020

Clinical Cancer Research

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“…Mutations in genes such as TP53 and PIK3R1 in endometrial cancer are correlated with tumor staging and survival [ 28 ]. Through next-generation sequencing (NGS) and analysis, we identified 59 somatic nucleotide mutations in 25 of the 53 examined tumor-related genes (Fig.…”

Section: Resultsmentioning

confidence: 99%

A clear cancer cell line (150057) derived from human endometrial carcinoma harbors two novel mutations

Chang

Ding

2020

BMC Cancer

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Background Cell lines are extremely useful for both basic and clinical research. Thus, establishing endometrial cancer cell lines with malignant histology is important. This study aimed to extensively characterize an endometrial clear cell carcinoma cell line. Methods This cell line, named 150,057, was derived from the endometrial clear cell cancer of a 63-year-old woman. The morphology, chromosomes, chemosensitivity, tumor markers, xenotransplantation characteristics, and cancer-related genes of the cell line were characterized. Results This cell line exhibited adequate growth, being passaged more than 70 times. The morphology of the cells was polygonal with a cobblestone-like appearance. Karyotyping of the cell line revealed a hypodiploid chromosomal number. 150057 cells expressed CA19–9 and CA125. The cell line was sensitive to doxorubicin, paclitaxel, carboplatin, and cisplatin. After the cells were transplanted into the subcutaneous region of non-obese diabetic-severe combined immunodeficiency mice, they generated xenograft tumors with similar histology as the original tumor. A total of 59 somatic nucleotide mutations were identified in 25 of the 53 examined tumor suppressor genes and oncogenes. Two novel mutations were found in FGFR3 and ARID1A. Conclusion We established and characterized an endometrial clear cell carcinoma cell line that may be useful in carcinogenesis and treatment research for endometrial cancer.

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“…Knowledge of the potential role of polymorphism of the TGFBR 3 gene encoding betaglycan and its relation to development of EC is elusive. Risk of endometrial cancer development is highly associated with different lifestyle and socio-demographic factors including obesity, onset of menarche, reproductive history, ethnicity and patient’s age [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Overweight, young age at menarche or nulliparity cause prolonged exposure to estrogens, which possess high proliferative potential, in particular to uterus lining.…”

Section: Discussionmentioning

confidence: 99%

Betaglycan Gene (TGFBR3) Polymorphism Is Associated with Increased Risk of Endometrial Cancer

Zakrzewski

Forma

Cygankiewicz

et al. 2020

JCM

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We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFβ co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15–4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20–4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18–34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT—OR = 4.04; 95% CI = 1.56–10.51; p = 0.0026; T—OR = 2.38; 95% CI = 1.16–4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54–15.07; p = 0.0116—Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29–8.15; p = 0.0328—Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180—CC vs. TT, p < 0.01; rs2296621—GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.

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Mutation frequencies in endometrial cancer patients of different ethnicities and tumor grades: An analytical study

Cited by 25 publications

References 51 publications

Genomic Profiling of Prostate Cancers from Men with African and European Ancestry

Genomic Profiling of Prostate Cancers from Men with African and European Ancestry

A clear cancer cell line (150057) derived from human endometrial carcinoma harbors two novel mutations

Betaglycan Gene (TGFBR3) Polymorphism Is Associated with Increased Risk of Endometrial Cancer

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