%0 Journal Article
%T Germline variants in pancreatic cancer patients with a personal or family history of cancer fulfilling the revised Bethesda guidelines.
%A Ohmoto A
%A Morizane C
%A Kubo E
%A Takai E
%A Hosoi H
%A Sakamoto Y
%A Kondo S
%A Ueno H
%A Shimada K
%A Yachida S
%A Okusaka T
%J J Gastroenterol
%V 53
%N 10
%D Oct 2018
%M 29667044
%F 6.772
%R 10.1007/s00535-018-1466-y
%X <B>BACKGROUND: </B>Pancreatic cancer (PC) is categorized as a neoplasm associated with Lynch syndrome; however, the precise proportion of PC patients harboring DNA mismatch repair genes (MMR genes) remains unclear, especially in the Asian population.<BR><B>METHODS: </B>Among 304 Japanese patients with pathologically proven pancreatic ductal adenocarcinoma, we selected 20 (6.6%) patients with a personal or family history involving first- or second-degree relatives fulfilling the revised Bethesda guidelines (RBG), defined as RBG-compatible cases. We analyzed germline variants in 21 genes related to a hereditary predisposition for cancer as well as clinical features in all 20 cases.<BR><B>RESULTS: </B>The RBG-compatible cases did not show any unique clinicopathological features. Targeted sequencing data revealed three patients carrying deleterious or likely deleterious variants. Specifically, these three patients harbored a nonsense variant in ATM, a frameshift variant in ATM, and a concurrent nonsense variant in PMS2 and missense variant in CHEK2 (double-mutation carrier), respectively. Although an MMR gene mutation was identified in only one of the 20 patients, up to 15% of the RBG-compatible PC cases were associated with germline deleterious or likely deleterious variants.<BR><B>CONCLUSIONS: </B>These findings showed that these guidelines could be useful for identifying PC patients with DNA damage repair genes as well as MMR genes.