期刊
CELL REPORTS
卷 15, 期 4, 页码 857-865出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.03.075
关键词
-
类别
资金
- KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources)
- KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH) [KL2 TR001100]
- Dana-Farber Cancer Institute Leadership Council
- Colon Cancer Alliance-AACR Fellowship for Biomarker Research [14-40-40-GIAN]
- Perry S. Levy Endowed Fellowship
- BroadNext10 grant
- BroadIgnite grant
- Project P Fund
- Blavatnik Family Foundation
- Friends of the Dana-Farber Cancer Institute
- NIH [U54 HG003067, K07 CA190673, K07 CA148894, K24 DK098311, R01 CA137178, R01 CA155010, P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, R01 CA151993, R35 CA197735, R01 CA118553, R01 CA168141, P50 CA127003]
Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据