PDF(Pubmed)
Abstract：
Although colorectal cancer (CRC) remains the second leading cause of cancer-related death in the United States, the overall incidence and mortality from the disease have declined in recent decades. In contrast, there has been a steady increase in the incidence of CRC in individuals under 50 years of age. Hereditary syndromes contribute disproportionately to early onset CRC (EOCRC). These include microsatellite instability high (MSI+) tumors arising in patients with Lynch Syndrome. However, most EOCRCs are not associated with familial syndromes or MSI+ genotypes. Comprehensive genomic profiling has provided the basis of improved more personalized treatments for older CRC patients. However, less is known about the basis of sporadic EOCRC. To define the genomic landscape of EOCRC we used DNA content flow sorting to isolate diploid and aneuploid tumor fractions from 21 non-hereditary cases. We then generated whole exome mutational profiles for each case and whole genome copy number, telomere length, and EGFR immunohistochemistry (IHC) analyses on subsets of samples. These results discriminate the molecular features of diploid and aneuploid EOCRC and provide a basis for larger population-based studies and the development of effective strategies to monitor and treat this emerging disease.
摘要：
尽管结直肠癌（CRC）仍然是美国癌症相关死亡的第二大原因，近几十年来，该疾病的总体发病率和死亡率有所下降。相比之下,在50岁以下的人群中,CRC的发病率稳步上升.遗传性综合征对早发性CRC(EOCRC)的贡献不成比例。这些包括在Lynch综合征患者中出现的微卫星不稳定性高(MSI+)肿瘤。然而,大多数EOCRC与家族综合征或MSI+基因型无关。全面的基因组分析为老年CRC患者提供了改进的更个性化治疗的基础。然而,对零星EOCRC的基础知之甚少。为了定义EOCRC的基因组格局，我们使用DNA含量流分选从21例非遗传性病例中分离出二倍体和非整倍体肿瘤部分。然后我们生成了每个病例的全外显子组突变谱和全基因组拷贝数，端粒长度,和EGFR免疫组织化学（IHC）分析样品的子集。这些结果区分了二倍体和非整倍体EOCRC的分子特征，并为更大规模的基于人群的研究以及开发监测和治疗这种新兴疾病的有效策略提供了基础。
