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

胃肿瘤22q染色体遗传变化分析

• 批准号: 11670225
• 负责人: TEI Shikofumi
• 金额: $ 2.37万
• 依托单位: The University of Tokyo (2000-2001)Jichi Medical University (1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670225/
• 关键词: Gastric tumor; 22q; p300; GIST; LOH; NF2

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.

1.对22例胃肠道间质瘤（GIST）（9例低危和13例高危）进行了杂合性丢失（洛）、微卫星不稳定性（MSI）和NF 2基因突变的研究。应用PCR-SSCP方法检测NF 2基因突变。22 q的洛缺失频率较高（17/22，77%）。在低危和高危肿瘤中的频率相似，与胃或肠起源无关。其他染色体上的额外洛缺失和两个以上位点的MSI是高危肿瘤的特征（P<0.05）。2例22 q-LOH病例中发现NF 2基因突变（外显子7剪接供体位点8bp缺失，外显子4 432位1bp插入，导致无义突变）。这些结果与c-kit基因突变之间没有明显的相关性，在22个肿瘤中有8个观察到c-kit基因突变。22 q上的抑制基因可能独立于c-kit基因突变而参与GIST的发生。NF 2在GIST的一小部分中作为肿瘤抑制因子发挥作用。胃癌组织中p300基因22 q13.1位点的杂合性丢失（洛）发生率较高，肠型（21/34）和弥漫型（30/46）的LOH发生率相当。而洛缺失仅在肠型中与临床分期及淋巴结转移显著相关。RT-PCR-SSCP分析显示，肠型和弥漫型p300基因突变分别为6/15和4/18，但仅肠型p300基因突变均伴有洛缺失。p300基因在肠型胃癌中具有抑癌基因的作用，而在弥漫型胃癌中不具有抑癌基因的作用。

项目成果

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)

Fukasawa,T. 等人：“胃肠道间质瘤中 14q 和 22q 等位基因丢失、NF2 突变和遗传不稳定性与 c-kit 突变无关。”日本癌症研究杂志。

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)

T.Fukasawa 等人：“胃肠道间质瘤中 14q 和 22q 等位基因丢失、NF2 突变和遗传不稳定性与 c-kit 突变无关”Jpn。