Cell Reports (Apr 2016)
Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma
- Marios Giannakis,
- Xinmeng Jasmine Mu,
- Sachet A. Shukla,
- Zhi Rong Qian,
- Ofir Cohen,
- Reiko Nishihara,
- Samira Bahl,
- Yin Cao,
- Ali Amin-Mansour,
- Mai Yamauchi,
- Yasutaka Sukawa,
- Chip Stewart,
- Mara Rosenberg,
- Kosuke Mima,
- Kentaro Inamura,
- Katsuhiko Nosho,
- Jonathan A. Nowak,
- Michael S. Lawrence,
- Edward L. Giovannucci,
- Andrew T. Chan,
- Kimmie Ng,
- Jeffrey A. Meyerhardt,
- Eliezer M. Van Allen,
- Gad Getz,
- Stacey B. Gabriel,
- Eric S. Lander,
- Catherine J. Wu,
- Charles S. Fuchs,
- Shuji Ogino,
- Levi A. Garraway
Affiliations
- Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Xinmeng Jasmine Mu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Sachet A. Shukla
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Zhi Rong Qian
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Ofir Cohen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Reiko Nishihara
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Samira Bahl
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Yin Cao
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Ali Amin-Mansour
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Mai Yamauchi
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Yasutaka Sukawa
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo 108-8345, Japan
- Chip Stewart
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Mara Rosenberg
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Kosuke Mima
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Kentaro Inamura
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Katsuhiko Nosho
- Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
- Jonathan A. Nowak
- Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Michael S. Lawrence
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Edward L. Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Andrew T. Chan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Jeffrey A. Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Eliezer M. Van Allen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Gad Getz
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Stacey B. Gabriel
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Eric S. Lander
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Catherine J. Wu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Charles S. Fuchs
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Shuji Ogino
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Levi A. Garraway
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- DOI
- https://doi.org/10.1016/j.celrep.2016.03.075
- Journal volume & issue
-
Vol. 15,
no. 4
pp. 857 – 865
Abstract
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.
