Noguchi T, Müller W, Wirtz H C, Willers R, Gabbert H E
Institute of Pathology, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
J Pathol. 1999 Aug;188(4):378-81. doi: 10.1002/(SICI)1096-9896(199908)188:4<378::AID-PATH378>3.0.CO;2-B.
The FHIT (fragile histidine triad) gene has been recently identified and cloned at chromosome 3p14.2 including FRA3B, the most common fragile site in the human genome. FHIT is suggested to be a candidate tumour suppressor gene in gastrointestinal tract tumours. To elucidate the role of the FHIT gene in gastric cancer, a total of 133 curatively R0-resected gastric carcinomas were investigated for loss of heterozygosity (LOH) at 3p14.2, using four polymorphic microsatellite loci (D3S1300, D3S1313, D3S1481, and D3S1234). LOH of the FHIT gene affecting at least one of the investigated loci was observed in 20 of 123 informative tumours (16.3 per cent). The presence of LOH was correlated neither with major prognostic factors such as pT category, pN category or vascular invasion, nor with histological type or grade of differentiation of the tumours. In addition, there were no differences in the prognosis between patients with gastric carcinomas showing LOH at the FHIT gene and patients with tumours lacking LOH at the FHIT gene. These findings suggest that LOH of the FHIT gene represents an event in the tumourigenesis of only a small subset of gastric carcinomas and does not correlate with tumour progression or prognosis.
FHIT（脆性组氨酸三联体）基因最近已在3号染色体p14.2区域被鉴定和克隆，该区域包含FRA3B，即人类基因组中最常见的脆性位点。FHIT被认为是胃肠道肿瘤中一个潜在的抑癌基因。为阐明FHIT基因在胃癌中的作用，我们利用四个多态性微卫星位点（D3S1300、D3S1313、D3S1481和D3S1234），对133例接受根治性R0切除的胃癌进行了3p14.2区域杂合性缺失（LOH）检测。在123例信息充分的肿瘤中，有20例（16.3%）观察到影响至少一个检测位点的FHIT基因LOH。LOH的存在与pT分期、pN分期或血管侵犯等主要预后因素均无相关性，也与肿瘤的组织学类型或分化程度无关。此外，FHIT基因出现LOH的胃癌患者与FHIT基因未出现LOH的肿瘤患者在预后方面并无差异。这些发现表明，FHIT基因的LOH仅代表一小部分胃癌肿瘤发生过程中的一个事件，与肿瘤进展或预后无关。
