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
From the Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.
City of Hope Comprehensive Cancer Center, Duarte, CA.
Pancreas. 2025 Mar 1;54(3):e171-e178. doi: 10.1097/MPA.0000000000002408.
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.
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.
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.
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.
黑人/非裔美国（B/AA）胰腺导管腺癌（PDAC）患者的临床结局比白人患者更差，且在基因组数据库中的代表性不足。我们旨在通过一个多样化的队列来扩展对PDAC体细胞景观的理解。
收集了24例手术切除的PDAC病例的福尔马林固定石蜡包埋标本，并记录了自我报告的种族/族裔信息。对恶性和良性组织进行了全外显子测序。生物信息学分析包括遗传血统推断和体细胞突变分析，并与公共数据集进行比较。
在24例病例中，17例被确定为B/AA种族；遗传血统分析证实撒哈拉以南非洲血统的比例大于47%。最常发生突变的基因包括KRAS、TP53、SMAD4和CDKN2A。将我们队列中的突变与主要为白人的公开可用数据集进行比较，结果显示ATM、RREB1、BRCA1/2、KDM6A、ARID1A、BRAF和MYC的突变频率更高（P < 0.04）。当按种族合并队列并进行分析时，未观察到突变频率差异，包括KRAS。
对B/AA和白人患者的PDAC肿瘤进行基因组分析表明，突变频率存在相似性。需要开展更大规模的研究，以进一步了解不同大陆亚人群的分子特征。本研究为在基因组数据库和临床试验中公平纳入不同患者提供了进一步的理论依据。
