Clonal Structures of Regionally Synchronous Gastric Adenomas and Carcinomas

• DOI: 10.1158/1078-0432.ccr-18-0345
• Publication Date: 2018-06-26T14:28:57Z
• Authors: Seung-Hyun Jung; Shin Young Kim; Chang Hyeok An; Sung Hak Lee; Eun Sun Jung; Hyeon-Chun Park; Min Sung Kim; Yeun-Jun Chung; Sug Hyung Lee
• Keywords: Adenoma; Aged, 80 and over; Male; 0301 basic medicine; DNA Copy Number Variations; Carcinogenesis; Carcinoma; Genomics; Middle Aged; Neoplasm Proteins; 3. Good health; Clonal Evolution; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Stomach Neoplasms; Mutation; Exome Sequencing; Disease Progression; Humans; Exome; Female; Aged

Purpose: Gastric adenoma (GA) is a premalignant lesion that precedes intestinal-type gastric carcinoma (GC). However, genetic progression mechanisms from GA to GC have not been clarified.Experimental Design: We performed whole-exome sequencing-based mutational analyses for 15 synchronous pairs of attached GAs and GCs.Results: There was no significant difference in the number driver mutations or copy-number alterations between GCs. Well-known TP53, APC, RNF43, RPL22 were recurrently detected GA/GC pairs. In addition, we discovered novel KDM6A, PREX2, FAT1, KMT2C, GLI3, hypermutation GAs, but did identify recurrent drivers GA-to-GC progression. Clonal structure revealed most exhibit parallel evolution with early divergence rather than stepwise during Of note, three cases identified as clonally nonrelated despite lack histologic differences. found differences dominant signatures 1, 6, 15, 17 trunks, branches, branches. Compared our previous work on colon adenoma/carcinoma genome structures, where trunk evolution, genomes showed different model many branches.Conclusions: The preferred sequence events might be more context-dependent Our results show nonclonal common already acquired distinct genomic alterations, suggesting caution diagnosis GC, especially residual cases. Clin Cancer Res; 24(19); 4715-25. ©2018 AACR.