Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues.
cancer evolution
diagnosis
genome instability
prognosis
repeats
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
20 08 2019
20 08 2019
Historique:
pubmed:
8
8
2019
medline:
24
3
2020
entrez:
8
8
2019
Statut:
ppublish
Résumé
Repetitive sequences are hotspots of evolution at multiple levels. However, due to difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content, beyond microsatellites, in proteomes and genomes directly from proteomic and genomic raw data. This method was applied to a wide range of tumors and normal tissues. We identify high similarity between repeat instability patterns in tumors and their patient-matched adjacent normal tissues. Nonetheless, tumor-specific signatures both in protein expression and in the genome strongly correlate with cancer progression and robustly predict the tumorigenic state. In a patient, the hierarchy of genomic repeat instability signatures accurately reconstructs tumor evolution, with primary tumors differentiated from metastases. We observe an inverse relationship between repeat instability and point mutation load within and across patients independent of other somatic aberrations. Thus, repeat instability is a distinct, transient, and compensatory adaptive mechanism in tumor evolution and a potential signal for early detection.
Identifiants
pubmed: 31387980
pii: 1908790116
doi: 10.1073/pnas.1908790116
pmc: PMC6708321
doi:
Substances chimiques
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
16987-16996Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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