Alteration of driver gene in hyperplastic polyp-associated gastric cancer

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19087
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: Luo Yi 奈良県立医科大学, 医学部, 博士研究員 (30633797)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 胃癌 / ドライバー遺伝子 / ピロリ菌

Outline of Final Research Achievements

To assess the early carcinogenesis of stomach, we examined hyperplastic foveolar polyps (HFP). The 22 HFPs contained 3 mild dysplasia, one moderate dysplasia, 3 severe dysplasia, and 2 cancers. Five cases of severe dysplasia and cancer showed papillotubular structure and marked accumulation of 8OHdG. All 5 cases is negative for H. pylori. Intestinal phenotype examined by CDX2, MUC2, CD10 was found only in a small part of the only two cases. In the five cases, mutation in BRAF codon 600 (V:GTG to E:GAG) was observed. The BRAF:V600E is known as a rare mutation in gastric cancer. To investigate the effect of H. pylori infection to BRAF mutation, A375 melanoma cell line carrying BRAF:V600E was transfected with CagA and continuously treated with EGF for 38 weeks. After treatment, A375 cells expressed CDX2. BRAF:V600E was still detected; however, vemurafenib sensitivity was disappeared. These data suggest that H. pylori infection abrogate the advantage of BRAF mutation.

Free Research Field

分子病理学