Tamura G, Sakata K, Nishizuka S, Maesawa C, Suzuki Y, Iwaya T, Terashima M, Saito K, Satodate R
Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
Genes Chromosomes Cancer. 1997 Sep;20(1):98-102.
The FHIT (fragile histidine triad) gene has been isolated from the chromosome region 3p14.2, which includes the fragile site locus FRA3B and the breakpoint of the t(3;8) of familial renal carcinoma. FHIT has been suggested to be a candidate tumor suppressor gene for digestive tract carcinomas. To evaluate the significance of FHIT gene abnormalities in gastric carcinogenesis, we examined the allelic status and transcripts of the gene in 23 primary gastric carcinomas as well as 7 gastric carcinoma cell lines. Four of the seven (57%) cell lines exhibited homozygous deletions of variable sizes at 3p14.2 all of which included D3S1300, which is located close to, or within, FRA3B. However, only 2 of 16 (13%) informative cases showed loss of heterozygosity at D3S1300 in the primary tumors. Direct analysis by reverse transcriptase polymerase chain reaction failed to reveal abnormal transcripts, including exon skipping and sequence changes, in the primary tumors or in the cell lines without homozygous deletions. These results suggest that FHIT gene abnormalities are infrequent in primary gastric carcinomas and that the frequent homozygous deletions seen in cell lines might simply reflect the plasticity of the genome at FRA3B under culture conditions.
脆性组氨酸三联体（FHIT）基因已从染色体区域3p14.2分离出来，该区域包括脆性位点FRA3B以及家族性肾癌中t(3;8)的断点。FHIT被认为是消化道癌的候选抑癌基因。为评估FHIT基因异常在胃癌发生中的意义，我们检测了23例原发性胃癌以及7种胃癌细胞系中该基因的等位基因状态和转录本。7种细胞系中有4种（57%）在3p14.2处出现大小不一的纯合缺失，所有这些缺失均包含靠近FRA3B或位于FRA3B内的D3S1300。然而，在16例有信息价值的原发性肿瘤病例中，只有2例（13%）在D3S1300处显示杂合性缺失。通过逆转录聚合酶链反应进行的直接分析未能在原发性肿瘤或无纯合缺失的细胞系中发现异常转录本，包括外显子跳跃和序列变化。这些结果表明，FHIT基因异常在原发性胃癌中并不常见，细胞系中常见的纯合缺失可能仅仅反映了在培养条件下FRA3B处基因组的可塑性。
