GERMLINE PATHOGENIC VARIANTS IN PATIENTS WITH PANCREATIC DUCTAL ADENOCARCINOMA AND EXTRA-PANCREATIC MALIGNANCIES: A NATIONWIDE DATABASE ANALYSIS.

IF 7.1 1区医学 Q1 PATHOLOGY Modern Pathology Pub Date : 2025-01-08 DOI:10.1016/j.modpat.2025.100709

Valentyna Kryklyva, Michael J Pflüger, Hicham Ouchene, Hanneke Volleberg-Gorissen, Arjen R Mensenkamp, Marianne A Jonker, Carlijn van de Water, Iris D Nagtegaal, Marjolijn J L Ligtenberg, Lodewijk A A Brosens

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. About 10% of affected individuals have an inherited component. Deleterious germline variants increase the lifetime risk for PDAC and are often associated with an elevated risk for extra-pancreatic malignancies. In this study, we aim to determine the prevalence and impact of germline pathogenic variants (gPVs) in patients with PDAC and extra-pancreatic malignancies. Using tissue samples and longitudinal data from a nationwide pathology database, we identified patients with PDAC and a set of seven extra-pancreatic malignancies to investigate the presence of gPVs in 25 cancer susceptibility genes with targeted next-generation sequencing. Of 473 PDAC patients with at least one extra-pancreatic malignancy, 75 (16%) had gPVs. These were predominantly in ATM (n=22), CDKN2A (n=14), BRCA2 (n=10), or CHEK2 (n=10) genes. The combination of PDAC and ovarian carcinoma carried the highest prevalence of gPVs (4 of 10; 40%), followed by PDAC and melanoma (15 of 53; 28%), and PDAC and gastric cancer (2 of 9; 22%). PDAC patients with certain extra-pancreatic malignancies carry a higher burden of gPVs than unselected PDAC cohorts. This is a group that very likely benefits from genetic testing since germline status can have important diagnostic and therapeutic implications for affected individuals and their family members.

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胰腺导管腺癌和胰腺外恶性肿瘤患者的种系致病变异：一个全国性的数据库分析。

胰腺导管腺癌（PDAC）是一种致命的疾病。大约10%的患者有遗传因素。有害的种系变异增加了PDAC的终生风险，并且通常与胰腺外恶性肿瘤的风险升高有关。在这项研究中，我们的目的是确定生殖系致病变异（gPVs）在PDAC和胰腺外恶性肿瘤患者中的患病率和影响。利用组织样本和来自全国病理数据库的纵向数据，我们确定了PDAC患者和一组7个胰腺外恶性肿瘤，通过靶向下一代测序研究gpv在25个癌症易感基因中的存在。在473例至少有一种胰腺外恶性肿瘤的PDAC患者中，75例（16%）有gpv。这些主要发生在ATM （n=22）、CDKN2A （n=14）、BRCA2 （n=10）或CHEK2 （n=10）基因中。PDAC合并卵巢癌患者gPVs患病率最高(4 / 10；40%)，其次是PDAC和黑色素瘤(53例中的15例；28%)， PDAC和胃癌(2 / 9；22%)。患有某些胰腺外恶性肿瘤的PDAC患者比未选择的PDAC患者携带更高的gpv负担。这是一个很可能从基因检测中受益的群体，因为生殖系状态对受影响的个人及其家庭成员具有重要的诊断和治疗意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Modern Pathology 医学-病理学

CiteScore

14.30

自引率

2.70%

发文量

174

审稿时长

18 days

期刊介绍： Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.