Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancer Biol Ther. 2012 Dec;13(14):1390-5. doi: 10.4161/cbt.22336. Epub 2012 Oct 10.
The pathogenesis of sporadic colorectal cancer involves distinct pathways, with characteristic genomic alterations. The first pathway, chromosome instability (CIN), is driven by APC mutations and is typified by Kras mutations, p53 mutation/loss of heterozygosity, and deletions at chromosome 18q. The second pathway is referred to as microsatellite instability (MSI), a genetic hallmark of the accumulated mutations that occur as a consequence of derangements in the mismatch repair genes. Finally, proximal colon cancers may involve methylation of a number of genes, which is frequently referred to as the CpG island methylator phenotype (CIMP), and are associated with B-raf mutations. The ability to stratify colorectal cancers by risk would be facilitated by the identification of polymorphisms that might be utilized as biomarkers. LIN28B is an RNA binding protein that is overexpressed in colon cancers. We find that LIN28B rs314277 is associated with significant recurrence of colorectal cancer in Stage II disease, which may have translational therapeutic implications.
散发性结直肠癌的发病机制涉及不同的途径,具有特征性的基因组改变。第一条途径是染色体不稳定性(CIN),由 APC 突变驱动,其特征是 Kras 突变、p53 突变/杂合性丢失和 18q 染色体缺失。第二条途径称为微卫星不稳定性(MSI),是由于错配修复基因紊乱而导致的累积突变的遗传标志。最后,近端结肠癌可能涉及多个基因的甲基化,这通常被称为 CpG 岛甲基化表型(CIMP),并与 B-raf 突变有关。通过识别可能用作生物标志物的多态性,可以方便地对结直肠癌进行分层。LIN28B 是一种在结肠癌中过度表达的 RNA 结合蛋白。我们发现 LIN28B rs314277 与 II 期疾病中结直肠癌的显著复发相关,这可能具有转化治疗意义。