Tamura G, Ogasawara S, Nishizuka S, Sakata K, Maesawa C, Suzuki Y, Terashima M, Saito K, Satodate R
Department of Pathology, Iwate Medical University School of Medicine, Japan.
Cancer Res. 1996 Feb 1;56(3):612-5.
Frequent loss of heterozygosity (LOH) on the long arm of chromosome 5 (5q) has been reported in many types of human malignancies, including gastric carcinoma. One of the targets of 5q-LOH in colorectal carcinoma is certainly the adenomatous polyposis coli (APC) gene on 5q21. However, other evidence has suggested the presence of another tumor suppressor gene in this region which may be inactivated in gastric carcinoma. In the present study, to determine the location of the putative tumor suppressor gene on 5q, LOH at nine microsatellite loci on 5q were investigated at 38 differentiated adenocarcinomas of the stomach that probably did not carry APC mutations. LOH at any locus on 5q occurred in 37% (14 of 38) of the tumors. Although many tumors exhibited large interstitial deletions on 5q that included the APC locus (5q21), we have identified minimum regions of deletion as the D5S428 locus and the interferon regulatory factor-1 (IRF-1) locus. Thus, at least two putative tumor suppressor genes, which play a crucial role in the genesis of differentiated adenocarcinoma of the stomach and are distinct from the APC gene, lie on 5q.
在包括胃癌在内的多种人类恶性肿瘤中,均有关于5号染色体长臂(5q)杂合性缺失(LOH)频发的报道。在结直肠癌中,5q-LOH的靶点之一无疑是位于5q21的腺瘤性息肉病 coli(APC)基因。然而,其他证据表明该区域存在另一种肿瘤抑制基因,其在胃癌中可能失活。在本研究中,为确定5q上假定的肿瘤抑制基因的位置,对38例可能未携带APC突变的胃分化腺癌中5q上的9个微卫星位点的LOH进行了研究。5q上任何位点的LOH发生在37%(38例中的14例)的肿瘤中。尽管许多肿瘤在5q上表现出包括APC位点(5q21)在内的大片段间质性缺失,但我们已将最小缺失区域确定为D5S428位点和干扰素调节因子-1(IRF-1)位点。因此,至少有两个假定的肿瘤抑制基因位于5q上,它们在胃分化腺癌的发生中起关键作用,且与APC基因不同。