In 1996, Goggins and colleagues demonstrated the importance of germline BRCA2 pathogenic variants in the development of apparently sporadic pancreatic ductal adenocarcinoma (PDAC). Previously, the group identified homozygous deletion of the 13q region in PDACs, enabling the identification of the BRCA2 gene. This 1996 article first revealed loss of BRCA2, both germline and somatic, as a key driver of PDAC at a time when there was still doubt if PDAC even had an inherited component. Contrary to the prevailing wisdom, not all individuals with inherited pathogenic BRCA2 variants had a family history of cancer. The innovative bedside-to-bench nature of this work revealed that individuals with these variants would be missed if genetic testing was limited only to those meeting the family history criteria. Therefore, Goggins and colleagues advocated that universal genetic testing may be indicated for pancreatic cancer at a time when genetic testing was in its infancy. Twenty-three years later, in 2019, universal testing for pancreatic cancer became standard of care in the United States. Additionally, this work and future-related publications by the Kern Laboratory set the stage for targeting BRCA2 and related DNA repair mutations in pancreatic cancer via a synthetic lethal therapeutic approach. The provocative discussion initiated by this team in this publication is still inspiring the field today. In this seminal publication, Goggins and colleagues profoundly impacted the direction of pancreatic cancer research, leading to a more sophisticated approach to designing earlier detection and precision treatment strategies for pancreatic cancer. See related article by Goggins and colleagues, Cancer Res 1996;56:5360–4

中文翻译：

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种系 BRCA2 致病变异在“明显散发性”胰腺癌中的关键作用


1996 年，Goggins 及其同事证明了种系 BRCA2 致病性变异在明显散发的胰腺导管腺癌 (PDAC) 发展中的重要性。此前，该小组鉴定出了 PDAC 中 13q 区域的纯合缺失，从而能够鉴定出 BRCA2 基因。这篇 1996 年的文章首次揭示了 BRCA2（种系和体细胞）的缺失是 PDAC 的关键驱动因素，当时人们仍然怀疑 PDAC 是否具有遗传成分。与普遍观点相反，并非所有携带遗传性致病性 BRCA2 变异的个体都有癌症家族史。这项工作的创新性从床边到工作台的性质表明，如果基因检测仅限于那些符合家族史标准的人，那么携带这些变异的个体就会被遗漏。因此，Goggins 及其同事主张，在基因检测还处于起步阶段时，通用基因检测可能适用于胰腺癌。二十三年后的 2019 年，胰腺癌的普遍检测成为美国的护理标准。此外，Kern 实验室的这项工作和未来相关的出版物为通过合成致死治疗方法靶向胰腺癌中的 BRCA2 和相关 DNA 修复突变奠定了基础。该团队在本出版物中发起的挑衅性讨论至今仍然鼓舞着该领域。在这篇开创性的出版物中，戈金斯和同事深刻地影响了胰腺癌的研究方向，导致了一种更复杂的方法来设计胰腺癌的早期检测和精准治疗策略。参见 Goggins 及其同事的相关文章，Cancer Res 1996；56:5360–4