Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Clin Gastroenterol Hepatol. 2014 Mar;12(3):377-81. doi: 10.1016/j.cgh.2013.12.007. Epub 2013 Dec 17.
Colon cancer develops and progresses as a consequence of abnormal cellular molecular changes, many of which result in mutant DNA. Modern molecular techniques allow examination of individual patient genetic data that ascribe risk, predict outcome, and/or modify an approach to therapy. DNA testing and molecular screening are in use today and are becoming a critical and necessary part of routine patient care. Assessing at-risk patients for hereditary colon cancer is predicted to move from individual gene testing that is commonly performed today to whole exome or whole genome sequencing, providing additional vast information of the patient's genome that might not be related to the colon cancer syndrome. Detecting mutant DNA from shed tumor cells in fecal material for colon cancer screening will increase in diagnostic accuracy over time, with improvements in the panel of mutant DNA being examined and through clinical testing. DNA mutations and other molecular changes detected directly from within the colon cancer help to inform and guide the physician for the best approach for optimal patient care and outcome. The use of epidermal growth factor receptor-targeted therapy in advanced colon cancer patients requires knowledge of the mutation status for KRAS and BRAF genes, and knowing the mutational status of PIK3CA may predict how patients respond to aspirin to prevent colon cancer recurrence. Biologically driven decision-making, or precision medicine, is becoming increasingly adopted for optimal care and outcome for colon cancer patients. Gastroenterologists will need to be increasingly aware.
结肠癌的发生和发展是由于细胞分子的异常变化,其中许多变化导致 DNA 突变。现代分子技术允许检查个体患者的遗传数据,这些数据可以确定风险、预测结果和/或改变治疗方法。DNA 测试和分子筛查目前正在使用,并成为常规患者护理的重要组成部分。评估遗传性结肠癌高危患者的方法预计将从目前常见的个体基因检测转向外显子组或全基因组测序,提供患者基因组中可能与结肠癌综合征无关的更多信息。随着对检测粪便中脱落肿瘤细胞的突变 DNA 的诊断准确性的提高,用于结肠癌筛查的技术将不断改进,突变 DNA 的检测面板也在不断改进,并通过临床试验进行检测。从结肠癌内部直接检测到的 DNA 突变和其他分子变化有助于为医生提供最佳的治疗方法,以实现最佳的患者护理和结果。表皮生长因子受体靶向治疗在晚期结肠癌患者中的应用需要了解 KRAS 和 BRAF 基因的突变状态,而了解 PIK3CA 的突变状态可能有助于预测患者对阿司匹林预防结肠癌复发的反应。基于生物学的决策,即精准医疗,正越来越多地应用于结肠癌患者的最佳护理和结果。胃肠病学家将需要越来越多地了解这一点。