In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4805-4805
Abstract:
Metastatic disease is the main cause of death for breast cancer patients, but it is still unclear whether primary tumor characteristics are predictive of the metastasis phenotype. Our aim was to investigate, by analyzing chromosomal structural variation, the clonal similarities between primary breast tumors and their matched distant metastases. For 11 patients, we performed low-coverage (∼10x) whole-genome sequencing on 11 primary breast tumors and 13 matched distant metastases to enumerate chromosomal rearrangements. The tumor genomes (n = 24) harbored a median of 85 (range 18-405) chromosomal rearrangements per tumor, with a median of 82 (26-310) in primaries compared to 87 (18-405) in distant metastases. Similarity between tumors was assessed based on presence or absence of chromosomal rearrangements. Concordance between matched primaries and distant metastases from the same patient was high, with a median of 89% rearrangements being shared (range 61-100%). Nearly all of the rearrangements were patient-specific, with very little overlap when comparing all possible pairings of tumors from different patients (median 3%). The tumors exhibited different genomic patterns of rearrangements: some carried events scattered throughout the genome while other tumors had events in densely clustered foci - chromothripsis-like hotspots - at a few chromosomal locations. Irrespective of the type of rearrangement profile of the tumor genomes, the patterns were highly conserved between the primary tumor and metastasis from the same patient, although in general metastases acquired additional rearrangement events. Our study suggests that analysis of structural variation in tumor genomes could be useful for identifying tumor origin, facilitating cancer detection via measurement of rearrangements in circulating tumor DNA, and estimating degree of relatedness between primary tumors and metastases. Moreover, our finding that distant metastases have a close clonal relationship to the primary tumor at the level of chromosomal structure is most consistent with chromosomal rearrangements being early events in breast cancer progression that remain stable during the development from a primary tumor to its distant metastasis. Citation Format: Man-Hung Tang, Malin Dahlgren, Christian Brueffer, Christof Winter, Yilun Chen, Eleonor Olsson, Martin Sjöström, Pär-Ola Bendahl, Emma Niméus-Malmström, Lao H. Saal, Åke Borg, Sofia K. Gruvberger-Saal. Whole genome sequencing of primary breast cancers and matched distant metastases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4805. doi:10.1158/1538-7445.AM2015-4805
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-4805
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
