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

1.对22例胃肠道间质瘤(9例低危和13例高危)进行了杂合性缺失(LOH)、微卫星不稳定性(MSI)和NF2基因突变检测。用21条染色体臂上的41个标记检测LOH和MSI，用聚合酶链式反应-单链构象多态性(PCR-SSCP)检测NF2基因突变。22q有较高频率的杂合性缺失(17/22，77%)。在低危和高危肿瘤中的频率相似，并且与胃或肠道来源无关。另外两个异常，其他染色体上额外的杂合性缺失和两个以上基因座的微卫星不稳定性，是高危肿瘤的特征(P&lt；0.05)。NF2基因突变2例，均为22q-LOH(外显子7剪接供体部位缺失8个碱基，外显子4 432位插入1个碱基，导致无义突变)。这些结果与c-kit基因突变无明显相关性，在22例肿瘤中有8例观察到c-kit基因突变。22q上的抑制基因可能独立于c-kit基因突变而参与GIST的发生发展。NF2在GIST的一小部分中作为肿瘤抑制因子发挥作用。杂合性缺失(LOH)多见于p300基因22q13.1位点，肠型(21/34)和弥漫型(30/46)的杂合性丢失频率相同。而LOH仅在肠型与晚期和淋巴结转移显著相关。RT-PCR-SSCP分析发现，p300基因突变存在于肠型(6/15)和弥漫型(4/18)，但所有突变均仅在肠型伴有杂合性缺失。P300基因在肠道中表现为抑癌基因，但在弥漫型胃癌中不表现为抑癌基因。

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.