Pancreas · 2025
Somatic Genomic Profiling of Pancreatic Ductal Adenocarcinomas From a Diverse Cohort of Patients.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Riner Andrea N, Velazquez-Villarreal Enrique I, Rajpara Seeta, Qian Jing, Jin Yuxin, Loza Donna, Akki Ashwin, Herremans Kelly M, Raj Rohit, Williams Terence M, Merchant Nipun, George Thomas J, Hughes Steven J, Stern Mariana C, Reams Renee, Redda Ken, Wilkie Diana J, Odedina Folakemi T, Chamala Srikar, Han Bo, Agyare Edward, Craig David W, Carpten John D, Trevino Jose G
Аннотация
OBJECTIVES: Black/African American (B/AA) pancreatic ductal adenocarcinoma (PDAC) patients have worse clinical outcomes than White patients and are underrepresented in genomic databases. We aimed to expand our understanding of the PDAC somatic landscape from a diverse cohort.
MATERIALS AND METHODS: Formalin-fixed paraffin-embedded specimens from 24 surgically resected PDAC cases were collected, with self-reported race/ethnicity. Whole exome sequencing was performed on malignant and benign tissue. Bioinformatics analysis included deduction of genetic ancestry and somatic mutational analysis, with comparisons to public datasets.
RESULTS: Out of 24 cases, 17 identified as B/AA race; genetic ancestry analysis confirmed proportions of Sub-Saharan African ancestry greater than 47%. The most commonly mutated genes included KRAS, TP53, SMAD4, and CDKN2A. Comparison of mutations in our cohort versus publicly available, predominantly White datasets showed higher mutation frequencies of ATM, RREB1, BRCA1/2, KDM6A, ARID1A, BRAF, and MYC (P < 0.04). When cohorts were combined and analyzed by race, no mutation frequencies differences were observed, including KRAS.
CONCLUSIONS: Genomic analysis of PDAC tumors from B/AA and White patients demonstrate similarities in mutation frequencies. Larger studies are needed to further understand molecular characterizations across continental subpopulations. This study provides further rationale for equitable representation of diverse patients in genomic databases and clinical trials.
MATERIALS AND METHODS: Formalin-fixed paraffin-embedded specimens from 24 surgically resected PDAC cases were collected, with self-reported race/ethnicity. Whole exome sequencing was performed on malignant and benign tissue. Bioinformatics analysis included deduction of genetic ancestry and somatic mutational analysis, with comparisons to public datasets.
RESULTS: Out of 24 cases, 17 identified as B/AA race; genetic ancestry analysis confirmed proportions of Sub-Saharan African ancestry greater than 47%. The most commonly mutated genes included KRAS, TP53, SMAD4, and CDKN2A. Comparison of mutations in our cohort versus publicly available, predominantly White datasets showed higher mutation frequencies of ATM, RREB1, BRCA1/2, KDM6A, ARID1A, BRAF, and MYC (P < 0.04). When cohorts were combined and analyzed by race, no mutation frequencies differences were observed, including KRAS.
CONCLUSIONS: Genomic analysis of PDAC tumors from B/AA and White patients demonstrate similarities in mutation frequencies. Larger studies are needed to further understand molecular characterizations across continental subpopulations. This study provides further rationale for equitable representation of diverse patients in genomic databases and clinical trials.