Dataset Information

Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset.

ABSTRACT:

Objective

Recent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS).

Methods

Archival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were analyzed and compared according to the stage and histological type. Additionally, survival effects of specific mutated genes were analyzed.

Results

Somatic mutation patterns of 38 genes were identified in 263 EC samples, and the most commonly mutated genes were PTEN and PIK3CA. PTEN was the most common in endometrioid histology, while PPP2R1A was the most commonly mutated gene in serous histology. The mutation rates of PPP2R1A and TP53 were significantly higher in advanced EC sample than in stage I samples (22.5% vs. 4.3% [p<0.001] and 8.4% vs. 1.4% [p=0.021], respectively). Survival analysis of the total population and endometrioid subgroup revealed that patients with PPP2R1A mutations had significantly shorter survival than did those without mutations (p=0.005 and p<0.001, respectively).

Conclusion

PPP2R1A mutations might have a role in dismal prognosis of advanced EC.

SUBMITTER: Hong JH

PROVIDER: S-EPMC9024183 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset.

Hong Jin Hwa JH Cho Hyun Woong HW Ouh Yung-Taek YT Lee Jae Kwan JK Chun Yikyeong Y Gim Jeong-An JA

Journal of gynecologic oncology 20220124 3

<h4>Objective</h4>Recent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS).<h4>Methods</h4>Archival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were ana ...[more]

PMID: 35128859

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Project description:Uterine Corpus Endometrial Carcinoma (UCEC) is a significant health concern with a complex genetic landscape impacting disease susceptibility and progression. This study aimed to unravel the spectrum of DNA repair gene mutations in Pakistani UCEC patients through Next Generation Sequencing (NGS) and explore their potential functional consequences via downstream analyses. NGS analysis of genomic DNA from 30 UCEC patients was conducted to identify clinically significant pathogenic mutations in DNA repair genes. This analysis revealed mutations in 4 key DNA repair genes: BRCA1, BRCA2, APC, and CDH1. Kaplan-Meier (KM) analysis was employed to assess the prognostic value of these mutations on patient overall survival (OS) in UCEC. To delve into the functional impact of these mutations, we performed RT-qPCR, immunohistochemistry (IHC), and western blot analyses on the mutated UCEC samples compared to their non-mutated counterparts. These results unveiled the up-regulation in the expression of the mutated genes, suggesting a potential association between the identified mutations and enhanced gene activity. Additionally, targeted bisulfite sequencing analysis was utilized to evaluate DNA methylation patterns in the promoters of the mutated genes. Strikingly, hypomethylation in the promoters of BRCA1, BRCA2, APC, and CDH1 was observed in the mutated UCEC samples relative to the non-mutated, indicating the involvement of epigenetic mechanisms in the altered gene expression. In conclusion, this study offers insights into the genetic landscape of DNA repair gene mutations in Pakistani UCEC patients. The presence of pathogenic mutations in BRCA1, BRCA2, APC, and CDH1, coupled with their down-regulation and hypermethylation, suggests a convergence of genetic and epigenetic factors contributing to genomic instability in UCEC cells. These findings enhance our understanding of UCEC susceptibility and provide potential avenues for targeted therapeutic interventions in Pakistani UCEC patients.

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Dataset Information

Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset.

Objective

Methods

Results

Conclusion

Publications

Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset.

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