Initial and crucial genetic events in intestinal‐type gastric intramucosal neoplasia

• DOI: 10.1002/path.5208
• Publication Date: 2018-11-26T09:15:52Z
• Authors: Hirofumi Rokutan; Hiroyuki Abe; Hiromi Nakamura; Tetsuo Ushiku; Erika Arakawa; Fumie Hosoda; Shinichi Yachida; Yosuke Tsuji; Mitsuhiro Fujishiro; Kazuhiko Koike; Yasushi Totoki; Masashi Fukayama; Tatsuhiro Shibata
• Keywords: MLH1

Abstract Gastric cancer (GC) is one of the most common and life‐threatening malignancies. The course disease tumor aggressiveness vary among GCs, although how early fate determined by what factors remains elusive. To solve this question, we collected 43 gastric intramucosal neoplasias (GINs), comprising dysplasia/intraepithelial neoplasia (D/IEN; a premalignant lesion) minute GC (miGC; ≤10 mm) intestinal histotype performed targeted deep DNA sequencing 67 GC‐related genes derived from large‐scale data. D/IEN was classified into low or high grade (LG‐D/IEN HG‐D/IEN). frequent mutations in D/IENs included APC (19/25; 76%), ARID2 (6/25; 24%) MUC6 (5/25; 20%). All LG‐D/IENs had mutation (12/12) hotspot affecting R1450 E1554 were noted both LG‐D/IEN HG‐D/IEN. always co‐occurred with mutation, whose variant allele frequency (TVAF) higher than that D/IEN. TP53 mutually exclusive ( p = 0.031 [main cohort], 0.025 [expanding cohort]) ‐mutated exclusively HG‐D/IEN (4/4). highly recurrent (11/14; 79%) MLH1‐positive miGCs detected even two microscopic lesions measuring 1 3 mm, respectively. Furthermore, TVAF analyses suggested initial event miGCs. In contrast, absent (0/4) MLH1‐negative small carcinoma (8–24 mm). Advanced data ) may affect potential cancerous progression This study revealed somatic mutational landscape GINs, report for first time precede other intestinal‐type GC. Our results also indicate molecular subtyping based on / would be high‐priority approach determining predicting malignant GIN, including Copyright © 2018 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.