Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing.

Author:
  • Man-Hung Eric Tang
  • Malin Dahlgren
  • Christian Brueffer
  • Tamara Tjitrowirjo
  • Christof Winter
  • Yilun Chen
  • Eleonor Olsson
  • Kun Wang
  • Therese Törngren
  • Martin Sjöström
  • Dorthe Grabau
  • Pär-Ola Bendahl
  • Lisa Rydén
  • Emma Niméus
  • Lao Saal
  • Åke Borg
  • Sofia Gruvberger
Publishing year: 2015
Language: English
Pages: 37169-37184
Publication/Series: Oncotarget
Volume: 6
Issue: 35
Document type: Journal article
Publisher: Impact Journals, LLC

Abstract english

To better understand and characterize chromosomal structural variation during breast cancer progression, we enumerated chromosomal rearrangements for 11 patients by performing low-coverage whole-genome sequencing of 11 primary breast tumors and their 13 matched distant metastases. The tumor genomes harbored a median of 85 (range 18-404) rearrangements per tumor, with a median of 82 (26-310) in primaries compared to 87 (18-404) in distant metastases. Concordance between paired tumors from the same patient was high with a median of 89% of rearrangements shared (range 61-100%), whereas little overlap was found when comparing all possible pairings of tumors from different patients (median 3%). The tumors exhibited diverse genomic patterns of rearrangements: some carried events distributed throughout the genome while others had events mostly within densely clustered chromothripsis-like foci at a few chromosomal locations. Irrespectively, the patterns were highly conserved between the primary tumor and metastases from the same patient. Rearrangements occurred more frequently in genic areas than expected by chance and among the genes affected there was significant enrichment for cancer-associated genes including disruption of TP53, RB1, PTEN, and ESR1, likely contributing to tumor development. Our findings are most consistent with chromosomal rearrangements being early events in breast cancer progression that remain stable during the development from primary tumor to distant metastasis.

Keywords

  • Cancer and Oncology

Other

Published
  • CREATE Health
  • Breast cancer Proteogenomics
  • ISSN: 1949-2553
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90