Dataset Information

Proteomic and Genomic Signatures of Repeat-instability in Cancer and Adjacent Normal Tissues

ABSTRACT: Repetitive 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovary

SUBMITTER: Tamar Geiger

LAB HEAD: Tamar geiger

PROVIDER: PXD012574 | Pride | 2020-06-02

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Fozzie_20180901_GB_UL-CS-FFPE-TMT-set1_1.raw	Raw
	Fozzie_20180901_GB_UL-CS-FFPE-TMT-set1_2.raw	Raw
	Fozzie_20180901_GB_UL-CS-FFPE-TMT-set1_3.raw	Raw
	Fozzie_20180901_GB_UL-CS-FFPE-TMT-set1_4.raw	Raw
	Fozzie_20180901_GB_UL-CS-FFPE-TMT-set1_5.raw	Raw

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Publications

Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues.

Persi Erez E Prandi Davide D Wolf Yuri I YI Pozniak Yair Y Barnabas Georgina D GD Levanon Keren K Barshack Iris I Barbieri Christopher C Gasperini Paola P Beltran Himisha H Faltas Bishoy M BM Rubin Mark A MA Geiger Tamar T Koonin Eugene V EV Demichelis Francesca F Horn David D

Proceedings of the National Academy of Sciences of the United States of America 20190806 34

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 ...[more]

PMID: 31387980

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