Han H S, Kim H S, Woo D K, Kim W H, Kim Y I
Department of Pathology, Seoul National University College of Medicine, Korea.
Anticancer Res. 2000 Sep-Oct;20(5A):2849-54.
The MEN1 gene locus is known to be partly responsible for the tumorigenesis of sporadic gastric neuroendocrine tumors, but the genetic events that drive the neoplastic process of this tumor remain largely unknown. In order to screen the tumor suppressor genes associated with the tumorigenesis of gastric neuroendocrine tumors, 15 neuroendocrine carcinomas and three carcinoid tumors in the stomach were analyzed for loss of heterozygosity (LOH) using 22 microsatellite markers. In our study, the gastric neuroendocrine tumors showed a high rate of LOH in chromosomes 8p (82%), 15q (58%), 17p (57%), llp (50%), 12p (50%) and 13q (50%). The mean fractional allelic loss (FAL) was higher in the neuroendocrine carcinoma components than in the adenocarcinoma components (0.42 versus 0.33, respectively). In four cases, the adenocarcinoma components showed discordant LOH patterns from those of the neuroendocrine counterparts in half of the informative chromosomes analyzed. Comparably, the gastric neuroendocrine carcinomas exhibited a higher LOH frequency on 8p and a lower LOH on 7q than did the gastric adenocarcinomas. It is suggested that chromosome 8p is the possible location of the tumor suppressor genes associated with the tumorigenesis of gastric neuroendocrine tumors.
已知MEN1基因位点部分参与散发性胃神经内分泌肿瘤的肿瘤发生过程,但驱动该肿瘤肿瘤形成过程的遗传事件仍 largely未知。为了筛选与胃神经内分泌肿瘤肿瘤发生相关的肿瘤抑制基因,使用22个微卫星标记对15例胃神经内分泌癌和3例胃类癌进行杂合性缺失(LOH)分析。在我们的研究中,胃神经内分泌肿瘤在染色体8p(82%)、15q(58%)、17p(57%)、11p(50%)、12p(50%)和13q(50%)显示出较高的LOH率。神经内分泌癌成分的平均等位基因缺失分数(FAL)高于腺癌成分(分别为0.42和0.33)。在4例病例中,腺癌成分在分析的半数信息染色体中显示出与神经内分泌对应成分不同的LOH模式。相比之下,胃神经内分泌癌在8p上的LOH频率高于胃腺癌,而在7q上的LOH频率低于胃腺癌。提示染色体8p可能是与胃神经内分泌肿瘤肿瘤发生相关的肿瘤抑制基因的位置。