Dong S M, Kim K M, Kim S Y, Shin M S, Na E Y, Lee S H, Park W S, Yoo N J, Jang J J, Yoon C Y, Kim J W, Kim S Y, Yang Y M, Kim S H, Kim C S, Lee J Y
Department of Pathology and Cancer Research Institute, Catholic University Medical College, Seoul, Korea.
Cancer Res. 1998 Sep 1;58(17):3787-90.
We analyzed somatic mutation and loss of heterozygosity (LOH) in the serine/threonine kinase 11 (STK11)/Peutz-Jeghers syndrome gene in 49 colorectal tumors in three different stages of a dysplasia-carcinoma sequence. We detected LOH in 10 of 19 (52.6%) informative colorectal cancers at loci D19S886 and/or D19S883, but no LOH was observed in 25 informative adenomas. We detected a total of 9 somatic mutations [7 of 13 (53.8%) left-sided colon cancers and 2 of 7 (28.6%) left-sided adenomas with high-grade dysplasia], but no mutations were detected in right-sided colon tumors. Of the nine mutations, one was a frameshift mutation (the same mutation detected in Peutz-Jeghers syndrome family previously), and the other eight were missense mutations. This results indicate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.
我们分析了发育异常-癌序列三个不同阶段的49例结直肠肿瘤中丝氨酸/苏氨酸激酶11（STK11）/黑斑息肉综合征基因的体细胞突变和杂合性缺失（LOH）情况。在19例信息充分的结直肠癌中，有10例（52.6%）在D19S886和/或D19S883位点检测到LOH，但在25例信息充分的腺瘤中未观察到LOH。我们共检测到9个体细胞突变[13例左侧结肠癌中有7例（53.8%），7例高级别发育异常的左侧腺瘤中有2例（28.6%）]，但右侧结肠肿瘤中未检测到突变。在这9个突变中，1个是移码突变（与之前在黑斑息肉综合征家族中检测到的突变相同），另外8个是错义突变。这些结果表明，STK11是一种肿瘤抑制基因，STK11的基因改变在左侧结肠癌发生中起重要作用。
