Interpretation of cancer mutations using a multiscale map of protein systems.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
A major goal of cancer research is to understand how mutations distributed across diverse genes affect common cellular systems, including multiprotein complexes and assemblies. Two challenges—how to comprehensively map such systems and how to identify which are under mutational selection—have hindered this understanding. Accordingly, we created a comprehensive map of cancer protein systems integrating both new and published multi-omic interaction data at multiple scales of analysis. We then developed a unified statistical model that pinpoints 395 specific systems under mutational selection across 13 cancer types. This map, called NeST (Nested Systems in Tumors), incorporates canonical processes and notable discoveries, including a PIK3CA-actomyosin complex that inhibits phosphatidylinositol 3-kinase signaling and recurrent mutations in collagen complexes that promote tumor proliferation. These systems can be used as clinical biomarkers and implicate a total of 548 genes in cancer evolution and progression. This work shows how disparate tumor mutations converge on protein assemblies at different scales.
Identifiants
pubmed: 34591613
doi: 10.1126/science.abf3067
pmc: PMC9126298
mid: NIHMS1796978
doi:
Substances chimiques
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabf3067Subventions
Organisme : NCI NIH HHS
ID : F30 CA236404
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA243885
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103504
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM132322
Pays : United States
Organisme : NIH HHS
ID : S10 OD026929
Pays : United States
Organisme : NCI NIH HHS
ID : F99 CA212456
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009979
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209988
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA212456
Pays : United States
Organisme : NIDCR NIH HHS
ID : U01 DE028227
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026870
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209891
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA239336
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA067754
Pays : United States
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