Lynch H T, Smyrk T
Department of Preventive Medicine, Creighton University School of Medicine, Omaha, NE 68178, USA.
Curr Opin Oncol. 1998 Jul;10(4):349-56. doi: 10.1097/00001622-199807000-00012.
Recent advances in hereditary nonpolyposis colorectal cancer (HNPCC) have been made based on the discovery early in this decade that germline mutations in genes responsible for repair of DNA mismatches formed the molecular basis for the syndrome. Several studies during the past year described the prevalence of germline mutations in those deemed at risk for HNPCC and helped define who should be tested for such mutations. Investigators are also beginning to make connections between genotype and phenotype; it appears that certain mutations are more likely than others to generate a broad spectrum of extracolonic tumors. Carcinogenetic mechanisms in HNPCC also received attention; evidence continues to accumulate that the critical somatic mutations driving malignant transformation in HNPCC (and in sporadic colorectal cancer with microsatellite instability) are different from the critical mutations seen in most colon cancers. Finally, several contributions dealt with the complicated question of how to manage germline carriers and affected individuals.
遗传性非息肉病性结直肠癌（HNPCC）在本十年初基于如下发现取得了新进展：负责修复DNA错配的基因中的种系突变构成了该综合征的分子基础。过去一年的多项研究描述了被认为有HNPCC风险者中种系突变的发生率，并有助于确定谁应该接受此类突变检测。研究人员也开始建立基因型与表型之间的联系；似乎某些突变比其他突变更有可能引发广泛的结肠外肿瘤。HNPCC中的致癌机制也受到了关注；越来越多的证据表明，驱动HNPCC（以及伴有微卫星不稳定性的散发性结直肠癌）发生恶性转化的关键体细胞突变与大多数结肠癌中所见的关键突变不同。最后，有几项研究探讨了如何管理种系携带者和患病个体这一复杂问题。
