散发性结直肠癌3号染色体等位基因杂合缺失

Loss of heterozygosity on chromosome 3 in sporadic colorectal carcinoma

目的 了解散发性结直肠癌 (SCRC) 3号染色体等位基因杂合缺失 (LOH)发生情况 ,探讨其与临床病理特征间的关系 ,并对 3号染色体上可能的SCRC相关基因进行初步定位。方法 用覆盖 3号染色体的 13个微卫星标记对 83例散发性结直肠癌进行LOH扫描分析。结果 3号染色体至少有两个位点发生LOH者占 39% (2 9/74) ,3p所选 4个位点中至少有一个发生LOH者占 37% (2 7/74) ,3q所选 9个位点中至少有一个发生LOH者占 5 3 % (39/74)。整条染色体上以D3S130 0 (3p14.2 )位点LOH率最高 ,达 5 4% (2 3/4 3)。 3qLOH在远端结直肠癌较近端高发。 3p及D3S130 0LOH阳性肿瘤多表现为浸润型生长和局部侵犯 ,并多发于大于 5 0岁的老年患者。结论 3号染色体存在散在分布及区域性高频等位基因LOH ,并与SCRC临床病理资料相关 ,提示其上SCRC相关基因的存在。高频LOH位点D3S130 0的发现 ,提示 3p14.2附近区域的FHIT基因可能作为肿瘤抑制基因在结直肠癌的发生发展中发挥作用。

Objective To study the loss of heterozygosity (LOH) on chromosome 3 in sporadic colorectal carcinoma (SCRC) and to explore the possible CRC related genes or loci. Methods LOH at 13 microsatellite loci spanning chromosome 3 were detected in 83 cases with SCRC. Results At least two loci LOH on chromosome 3 were detected in 29 of 74 (39%) cases. In 27 of 74 (37%) cases at least one locus LOH was detected on 3p, and in 39 of 74 (53%) cases at least one of 9 loci had LOH on 3q. Of the 13 loci examined, D3S1300 (3p14.2) was identified as the locus with most frequent LOH. 3q LOH was found to occur in distal CRCs more often than those proximal. Tumors with 3p and/or D3S1300 LOH had a tendency of local invasion, and occurred more often in patients older than 50 years. Conclusion LOH on chromosome 3, dispersed with high frequency at several loci, was correlated with clinico pathology of SCRC, indicating the existence of SCRC related genes on it. The discovery of D3S1300 locus with highly frequent LOH suggested that FHIT gene located in this region might act as a candidate tumor suppressor gene in the development of colorectal carcinoma.