Abstract 119: Genomic analysis of remnant gastric adenocarcinoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.119-119
• Main Authors: da Silva, Edaise M., Won, Helen H., Torrence, Dianne, Coit, Daniel, Berger, Michael F., Tang, Laura
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-119

Introduction: Prior to pharmaceutical treatment of gastroduodenal ulcer disease, partial gastrectomy was performed for the management of ulcer disease complicated by bleeding (PUD). The proposed mechanism for the development of gastric cancer in this setting is the chronic irritation of the mucosa by duodenal reflux into the gastric remnant. The aim of this study is to characterize the genetic profile of remnant gastric carcinoma (RGC). Material and Methods: Thirty cases of RGC developed in the setting of prior partial gastrectomy for PUD and without neoadjuvant chemotherapy were retrospectively collected from the institution database. Histopathological evaluation was performed to ensure >80% tumor cellularity with matching normal gastric mucosa prior to DNA extraction. Ultra-deep targeted sequencing of the thirty matched pairs was performed using the MSK-IMPACT assay (Integrated Mutation Profiling of Actionable Cancer Targets) to identify mutations and copy number alterations in a common set of 410 cancer-associated genes. MSK-IMPACT data from previously sequenced 45 sporadic gastric carcinomas (GC) was used as comparison. Results: The cohort consisted of 22 (73%) males and 8 (27%) females with the mean age of 73 years. The median interval between PUD and RGC resections was 34.8 years (7-60 years). By Lauren's classification, 60% of the tumors were intestinal, 23% diffuse and 17% mixed. Most of the tumors (47%) were poorly differentiated and stage II (40%). MSK-IMPACT sequencing revealed 299 total somatic alterations occurring in 148 of 410 targeted genes with a median number of non-synonymous somatic mutations and copy number events of 3 and 1 per patient, respectively. Of the 207 total mutations, 27.5% were hotspot COSMIC and 23.2% were loss-of-function mutations. Recurrent genomic events included mutually exclusive mutations in TP53 (33%) and amplifications in MDM2 (26%), alterations in the ERBB family genes (37%), ARID1A (16%), KMT2D (13%), CDH1 (13%), and CDK4 (13%). In addition, actionable alterations in PIK3CA (10%), FGFR1 (4%), PTEN (4%), and concurrent hotspot KRAS mutations and inactivation of p15/p16 (10%) were observed. Compared to the sporadic GC cases, RGC cases presented differences in the landscape and recurrence of alterations. Conclusion: The pathogenesis of RGC is likely associated with the prolonged exposure of the gastric mucosa to gastroduodenal contents. The mean age of patients may also exert effects on the development of the RGC.