Analysis of genetic change of chromosome 22q in gastric tumor.

• Project/Area Number: 11670225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo (2000-2001); Jichi Medical University (1999)
• Principal Investigator: TEI Shikofumi The University of Tokyo, Graduate School of Medicine, assistant professor, 大学院・医学系研究科, 講師 (90285768)
• Co-Investigator(Kenkyū-buntansha): FUKAYAMA Masashi The University of Tokyo, Graduate School of Medicine, professor, 大学院・医学系研究科, 教授 (70281293)
• Project Period (FY): 1999 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: Gastric tumor / 22q / p300 / GIST / LOH / NF2

Research Abstract

1. Loss of heterozygosity (LOH), microsatellite instability (MSI) and NF2 gene mutation were investigated in 22 gastrointestinal stromal tumors (GIST) (9 low-risk and 13 high-risk tumors). LOH and MSI were evaluated using 41 markers on 21 chromosomal arms, and NF2 gene mutation was examined by PCR-SSCP. High frequency of LOH was observed on 22q (17/22, 77%). The frequencies were similar in low-risk and high-risk tumors, and were unrelated with gastric or intestinal origin. Two other abnormalities, additional LOH on other chromosomes and MSI at more than two loci, were characteristic of the high-risk tumors (P<0.05). NF2 gene mutation was identified in two cases showing 22q-LOH (8 bp deletion on the splice donor site of exon 7, and 1 bp insertion at positon 432 of exon 4, which resulted in nonsense mutation). There was no significant correlation between these results and c-kit gene mutation, which was observed in 8 of 22 tumors. Suppressor genes on 22q may be involved, independently of c-kit gene mutation, in the development of GIST. NF2 contributes as a tumor suppressor in a small subset of GIST.
2. Loss of heterozygosity (LOH) was frequently observed at the 22q13.1 Iocus containing the p300 gene in gastric carcinomas, with an equal frequency in the intestinal (21/34) and diffuse (30/46) types. However, LOH was significantly correlated with advanced stage and lymph node metastasis only in the intestinal type. Using RT-PCR-SSCP analysis, mutations of the p300 gene were identified in the intestinal (6/15) and in the diffuse (4/18) types, but all of the mutations were accompanied by LOH only in the intestinal type. The p300 gene behaves as tumor suppressor gene in the intestinal, but not in the diffuse type of gastric carcinoma.

Research Products

• [Publications] T.Fukasawa, et al.: "Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor"Jpn. J. Cancer Res.. 91. 1241-1249 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukasawa T, Chong J.-M., Sakurai S, Koshiishi N, Ikeno R, Tanaka A, Matsumoto Y, Hayashi Y, Koike M., and Fukayama M: "Allelic Loss of 14q and 22q, NF2 Mutation, and Genetic Instability Occur Independently of c-kit Mutation in Gastrointestinal Stromal Tumor"Jpn. J. Cancer Res.. 91. 1241-1249 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fukasawa,T., et al.: "Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor."Japanese journal of cancer research. 91. 1241-1249 (2000)