Author:
Persi Erez,Prandi Davide,Wolf Yuri I.,Pozniak Yair,Barbieri Christopher,Gasperini Paola,Beltran Himisha,Faltas Bishoy M.,Rubin Mark A.,Geiger Tamar,Koonin Eugene V.,Demichelis Francesca,Horn David
Abstract
SummaryRepetitive sequences are hotspots of evolution at multiple levels. However, due to technical 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 of proteomes and genomes, directly from proteomic and genomic raw sequence data, and applied it to analyze a wide range of tumors and normal tissues. We identify high similarity between the repeat-instability in tumors and their patient-matched normal tissues, but also tumor-specific signatures, both in protein expression and in the genome, that 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 find an inverse relationship between repeat-instability and point mutation load, within and across patients, and independently of other somatic aberrations. Thus, repeat-instability is a distinct, transient and compensatory adaptive mechanism in tumor evolution.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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