Forster L F, Defres S, Goudie D R, Baty D U, Carey F A
Department of Pathology and Genetics, Ninewells Hospital, Scotland, UK.
J Clin Pathol. 2000 Oct;53(10):791-3. doi: 10.1136/jcp.53.10.791.
To explore the role of the Peutz-Jeghers gene (LKB1) in sporadic breast and colon cancers.
Thirty consecutive sporadic carcinomas of the breast and 23 of the colon were selected. DNA was extracted from paraffin wax embedded tissue and analysed for loss of heterozygosity (LOH) at microsatellite markers D19S886 and D19S565 close to the LKB1 gene. Tumours showing LOH were screened for LKB1 mutations by single strand conformational polymorphism (SSCP).
Five breast carcinomas showed LOH (21% and 7% of those informative for D19S886 and D19S565, respectively). Five of the colorectal carcinomas showed LOH (15% and 36% of those informative for D19S886 and D19S565, respectively), with one sample showing allele loss with both markers. Screening of these 10 carcinomas by SSCP identified one migrational shift but sequencing revealed an intronic polymorphism only. Therefore, no coding mutations were found in these carcinomas.
These findings suggest that although allele loss at the LKB1 locus occurs relatively frequently in sporadic breast and colon cancers, mutations do not seem to be a feature.
探讨黑斑息肉综合征基因（LKB1）在散发性乳腺癌和结肠癌中的作用。
选取30例连续的散发性乳腺癌和23例结肠癌。从石蜡包埋组织中提取DNA，并分析靠近LKB1基因的微卫星标记D19S886和D19S565处的杂合性缺失（LOH）。通过单链构象多态性（SSCP）对显示LOH的肿瘤进行LKB1突变筛查。
5例乳腺癌显示LOH（分别占D19S886和D19S565信息性样本的21%和7%）。5例结肠直肠癌显示LOH（分别占D19S886和D19S565信息性样本的15%和36%），其中1个样本在两个标记处均显示等位基因缺失。通过SSCP对这10例癌进行筛查，发现1个迁移改变，但测序仅显示内含子多态性。因此，在这些癌中未发现编码突变。
这些发现表明，尽管LKB1基因座的等位基因缺失在散发性乳腺癌和结肠癌中相对频繁发生，但突变似乎并非其特征。
