ArticleScience advances2026
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
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Authors and funding
21 authors.
Pushpamali De SilvaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0747-5637
Samantha FitzgeraldDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7676-0645
Jules CazaubielDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0009-0007-1992-3197
Kristin QianLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-5016-0112
Matan HofreeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8368-0299
Jia-Ren LinLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4702-7705
Roxanne PelletierLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Mariana Lopez LeonLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4599-7719
Phuong Vu Mai HoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0009-0008-9693-6730
Yasutoshi TakashimaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Juha P VäyrynenTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland.ORCID 0000-0002-8683-2996
Kosuke MatsudaDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0009-0009-5125-1129
Tomotaka UgaiDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0182-5269
Dane Ford-RoshonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-5197-7458
Pratyusha BalaHarvard Medical School, Boston, MA, USA.ORCID 0000-0001-7686-4700
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-2349-2656
Kimmie NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0631-1494
Jonathan A NowakDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0943-7407
Shuji OginoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3909-2323
Peter K SorgerLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3364-1838
Marios GiannakisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9012-6982
Funding
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8MValidity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI FUCHS, CHARLES S · 1991 to 2009
$41.8MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MCancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0MCancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5MProject 2U54CA224068 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CORCORAN, RYAN BRUCE, FLAHERTY, KEITH T · 2017 to 2021
$6.3MAccelerating Transdisciplinary Epidemiology of Colorectal CancerR35CA197735 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2015 to 2021
$6.0MEpigenetic Events and Colorectal Cancer EpidemiologyR01CA151993 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2010 to 2014
$2.6M(PQ3) The role of damaged DNA in inter-individual variation of tumor immunityR01CA208756 · NCI · BROAD INSTITUTE, INC. · PI HACOHEN, NIR · 2016 to 2020
$2.6MHarnessing DNA methylation in peripheral blood for improved colorectal cancer preventionR01CA285851 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marios Giannakis, Mingyang Song · 2024 to 2026
$2.0MIntegration of Immunology and Microbiology into Molecular Pathological Epidemiology of Colorectal CancerR50CA274122 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI UGAI, TOMOTAKA · 2023 to 2025
$506kNCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA208756NCI NIH HHS R01 CA285851NCI NIH HHS R35 CA197735NCI NIH HHS R50 CA274122NCI NIH HHS U01 CA167552NCI NIH HHS U54 CA224068NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA186107
Abstract
The RNF43 p.G659fs (
Indexed as
Colorectal NeoplasmsDNA-Binding ProteinsHistocompatibility Antigens Class IKiller Cells, NaturalMicrosatellite InstabilityPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesUbiquitin-Protein LigasesCell Line, TumorGene Expression Regulation, NeoplasticHLA-E AntigensHumansMutationUp-RegulationDNA-Binding ProteinsHistocompatibility Antigens Class IHLA-E AntigensMTOR protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesUbiquitin-Protein Ligases
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.