a Department of Pathology , Radboud Institute for Molecular Life Sciences, Radboud university medical center , Nijmegen , The Netherlands.
b Department of Medical Oncology , University Medical Center Utrecht, Utrecht University , Utrecht , The Netherlands.
Cancer Biol Ther. 2019;20(7):949-955. doi: 10.1080/15384047.2019.1595274. Epub 2019 Apr 19.
Acinar cell carcinoma (ACC) is a rare pancreatic neoplasm with dismal prognosis. Insights into the molecular basis of ACC can pave the way for the application of more effective, personalized therapies and detection of patients with hereditary predisposition. Molecular analysis revealed a germline (and ) mutation in a patient with a rare pancreatic ACC with extensive intraductal growth. Somatic loss of the wild-type allele in the tumor indicated the causal relationship of ACC with the germline defect. A thorough literature review identified another nine ACCs associated with germline mutation and two ACCs associated with germline mutation, resulting in a prevalence of germline mutations in almost 7% of ACCs. Moreover, somatic alterations are reported in 16% of sporadic ACCs. Overall, about one fifth (22%) of all pancreatic ACCs exhibit BRCA1/2 deficiency. This study underscores the important role of mutations in pancreatic ACC. All ACC patients should undergo genetic testing for mutations to identify carriers of pathogenic variants. This will allow to select patients that can benefit from targeted therapies directed against -deficient tumors and is also crucial as a referral to genetic screening for the relatives of affected individuals carrying germline alterations. ACC: acinar cell carcinoma; HBOC: Hereditary Breast and Ovarian Cancer; LOH: loss of heterozygosity; PARP: poly (ADP-ribose) polymerase; PDAC: pancreatic ductal adenocarcinoma; PP: pancreatic panniculitis; SD: standard deviation; WES: whole-exome sequencing.
腺泡细胞癌 (ACC) 是一种罕见的胰腺肿瘤，预后较差。深入了解 ACC 的分子基础可以为应用更有效、更个性化的治疗方法和检测遗传性易感性患者铺平道路。分子分析显示，一名罕见的具有广泛管内生长的胰腺 ACC 患者存在种系突变。肿瘤中野生型等位基因的体细胞缺失表明 ACC 与种系缺陷有因果关系。通过全面的文献回顾，确定了另外 9 例与种系突变相关的 ACC 和 2 例与种系突变相关的 ACC，导致种系突变在近 7%的 ACC 中普遍存在。此外，报道了 16%的散发性 ACC 存在体细胞改变。总体而言，大约五分之一（22%）的所有胰腺 ACC 表现出 BRCA1/2 缺陷。这项研究强调了突变在胰腺 ACC 中的重要作用。所有 ACC 患者都应接受种系突变检测，以确定致病性变异的携带者。这将使那些可以受益于针对 -缺陷肿瘤的靶向治疗的患者得到选择，并且对于携带种系改变的受影响个体的亲属进行遗传筛查也至关重要。ACC：腺泡细胞癌；HBOC：遗传性乳腺癌和卵巢癌；LOH：杂合性丢失；PARP：多聚（ADP-核糖）聚合酶；PDAC：胰腺导管腺癌；PP：胰腺 panniculitis；SD：标准偏差；WES：全外显子组测序。
