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dc.contributor.authorGrasso, Catherine S.
dc.contributor.authorGiannakis, Marios
dc.contributor.authorWells, Daniel K.
dc.contributor.authorHamada, Tsuyoshi
dc.contributor.authorMu, Xinmeng Jasmine
dc.contributor.authorQuist, Michael
dc.contributor.authorNowak, Jonathan A.
dc.contributor.authorNishihara, Reiko
dc.contributor.authorQian, Zhi Rong
dc.contributor.authorInamura, Kentaro
dc.contributor.authorMorikawa, Teppei
dc.contributor.authorNosho, Katsuhiko
dc.contributor.authorAbril-Rodriguez, Gabriel
dc.contributor.authorConnolly, Charles
dc.contributor.authorEscuin-Ordinas, Helena
dc.contributor.authorGeybels, Milan S.
dc.contributor.authorGrady, William M.
dc.contributor.authorHsu, Li
dc.contributor.authorHu-Lieskovan, Siwen
dc.contributor.authorHuyghe, Jeroen R.
dc.contributor.authorKim, Yeon Joo
dc.contributor.authorKrystofinski, Paige
dc.contributor.authorLeiserson, Mark D.M.
dc.contributor.authorMontoya, Dennis J.
dc.contributor.authorNadel, Brian B.
dc.contributor.authorPellegrini, Matteo
dc.contributor.authorPritchard, Colin C.
dc.contributor.authorPuig-Saus, Cristina
dc.contributor.authorQuist, Elleanor H.
dc.contributor.authorRaphael, Ben J.
dc.contributor.authorSalipante, Stephen J.
dc.contributor.authorShin, Daniel Sanghoon
dc.contributor.authorShinbrot, Eve
dc.contributor.authorShirts, Brian
dc.contributor.authorShukla, Sachet
dc.contributor.authorStanford, Janet L.
dc.contributor.authorSun, Wei
dc.contributor.authorTsoi, Jennifer
dc.contributor.authorUpfill-Brown, Alexander
dc.contributor.authorWheeler, David A.
dc.contributor.authorWu, Catherine J.
dc.contributor.authorYu, Ming
dc.contributor.authorZaidi, Syed H.
dc.contributor.authorZaretsky, Jesse M.
dc.contributor.authorGabriel, Stacey
dc.contributor.authorLander, Eric Steven
dc.contributor.authorGarraway, Levi A.
dc.contributor.authorHudson, Thomas J.
dc.contributor.authorFuchs, Charles S.
dc.contributor.authorRibas, Antoni
dc.contributor.authorOgino, Shuji
dc.contributor.authorPeters, Ulrike
dc.date.accessioned2020-05-28T15:42:07Z
dc.date.available2020-05-28T15:42:07Z
dc.date.issued2018-03
dc.date.submitted2018-02
dc.identifier.issn2159-8274
dc.identifier.issn2159-8290
dc.identifier.urihttps://hdl.handle.net/1721.1/125550
dc.description.abstractTo understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability–high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This largescale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion. SIGNIFICANCE: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not.en_US
dc.language.isoen
dc.publisherAmerican Association for Cancer Research (AACR)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1158/2159-8290.cd-17-1327en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleGenetic Mechanisms of Immune Evasion in Colorectal Canceren_US
dc.typeArticleen_US
dc.identifier.citationGrasso, Catherine S. et al. "Genetic Mechanisms of Immune Evasion in Colorectal Cancer." Cancer Discovery 8, 6 (March 2018): 730–49 © 2018 American Association for Cancer Researchen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentBroad Institute of MIT and Harvarden_US
dc.relation.journalCancer Discoveryen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-01-22T18:09:31Z
dspace.date.submission2020-01-22T18:09:33Z
mit.journal.volume8en_US
mit.journal.issue6en_US
mit.metadata.statusComplete


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