Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues Academic Article uri icon

Overview

MeSH Major

  • Adenocarcinoma
  • Clonal Evolution
  • Computational Biology
  • Lung Neoplasms
  • Melanoma
  • Prostatic Neoplasms

abstract

  • 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.

publication date

  • August 20, 2019

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1073/pnas.1908790116

PubMed ID

  • 31387980

Additional Document Info

start page

  • 16987

end page

  • 16996

volume

  • 116

number

  • 34