Aitchison Alan, Hakkaart Christopher, Day Robert C, Morrin Helen R, Frizelle Frank A, Keenan Jacqueline I
Department of Surgery, University of Otago Christchurch, Christchurch 8011, New Zealand.
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand.
Cancers (Basel). 2020 Dec 18;12(12):3829. doi: 10.3390/cancers12123829.
While overall colorectal cancer (CRC) cases have been declining worldwide there has been an increase in the incidence of the disease among patients under 50 years of age. Mutation of the gene is a common early event in CRC but is reported at lower rates in early-onset colorectal cancer (EOCRC) than in older patients. Here we investigate the mutation status of a cohort of EOCRC patients in New Zealand using a novel sequencing approach targeting regions of the gene encompassing the vast majority of known mutations. Using this strategy we find a higher rate (72%) of mutation than previously reported in EOCRC with mutations being spread throughout the gene rather than clustered in hotspots as seen with sporadic mutations in older patients. The rate of mutations falling within hotspots was similar to those previously seen in EOCRC and as such our study has implications for sequencing strategies for EOCRC patients. Overall there were low rates of both loss of heterozygosity and microsatellite instability whereas a relatively high rate (40%) of promoter methylation was found, possibly reflecting increasing exposure of young people to pro-oncogenic lifestyle factors.
虽然全球范围内结直肠癌（CRC）的总体病例数一直在下降，但50岁以下患者中该疾病的发病率却有所上升。该基因的突变是CRC常见的早期事件，但在早发性结直肠癌（EOCRC）中的报告发生率低于老年患者。在此，我们使用一种针对该基因区域的新型测序方法，对新西兰一组EOCRC患者的该基因突变状态进行了研究，该区域涵盖了绝大多数已知的该基因突变。采用这种策略，我们发现该基因突变率（72%）高于先前报道的EOCRC，且突变分布于整个基因，而非像老年患者散发性突变那样聚集在热点区域。热点区域内的突变率与先前在EOCRC中所见相似，因此我们的研究对EOCRC患者的测序策略具有启示意义。总体而言，杂合性缺失和微卫星不稳定性的发生率都较低，而该基因启动子甲基化率相对较高（40%），这可能反映出年轻人接触促癌生活方式因素的情况增加。
