Rhesus Macaque Model of Mismatch Repair-Deficient Colorectal Cancer (RNA-Seq). Rhesus Macaque Model of Mismatch Repair-Deficient Colorectal Cancer (RNA-Seq)

Colorectal cancer (CRC) remains the third most common cancer in the US, with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1. DNA methylation and transcriptome analysis was used to evaluate the rhesus macaque as a model organism to study carcinogenesis, develop immunotherapies and vaccines, and implement chemoprevention approaches pertinent to sporadic MSI-H and LS CRC in humans. NIH grant(s): Grant ID: 5 P30 CA016672-44 Grant title: Cancer Center Support Grant Affiliation: The University of Texas MD Anderson Cancer Center Grantor: NCI Overall design: We performed RNA-Seq in 21 colorectal tumors and twenty matched normal mucosa samples

结直肠癌（Colorectal cancer, CRC）仍是美国第三大常见癌症，其中15%的病例表现为微卫星不稳定（Microsatellite Instability, MSI），该类型由林奇综合征（Lynch Syndrome, LS）或MLH1启动子体细胞超甲基化引发。本机构的恒河猴队列自发罹患错配修复缺陷（mismatch repair deficient, MMRd）结直肠癌，其中相当比例的个体携带MLH1基因致病性种系突变。研究团队通过DNA甲基化和转录组分析，评估恒河猴作为模式生物的应用价值，以用于研究致癌机制、开发免疫疗法与疫苗，以及实施针对人类散发性MSI-H及林奇综合征相关结直肠癌的化学预防策略。
美国国立卫生研究院（National Institutes of Health, NIH）资助项目：
资助编号：5 P30 CA016672-44
资助标题：癌症中心支持基金
所属机构：德克萨斯大学MD安德森癌症中心（The University of Texas MD Anderson Cancer Center）
资助方：美国国家癌症研究所（National Cancer Institute, NCI）
实验整体设计：本研究对21例结直肠肿瘤样本及20例配对正常黏膜样本开展了RNA测序（RNA-Seq）