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Exome sequencing of contralateral breast cancer identifies metastatic disease

Klevebring, Daniel; Lindberg, Johan; Rockberg, Julia; Hilliges, Camilla; Hall, Per; Sandberg, Maria LU and Czene, Kamila (2015) In Breast Cancer Research and Treatment 151(2). p.24-319
Abstract

Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and... (More)

Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Alleles, Breast Neoplasms, Exome, Female, High-Throughput Nucleotide Sequencing, Humans, Mutation, Neoplasm Metastasis, Prognosis, Registries, Journal Article
in
Breast Cancer Research and Treatment
volume
151
issue
2
pages
6 pages
publisher
Springer
external identifiers
  • scopus:84937758852
ISSN
1573-7217
DOI
10.1007/s10549-015-3403-6
language
English
LU publication?
no
id
922d0516-c965-4185-9f1e-008837676a02
date added to LUP
2017-10-16 08:59:40
date last changed
2017-11-05 05:23:47
@article{922d0516-c965-4185-9f1e-008837676a02,
  abstract     = {<p>Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases.</p>},
  author       = {Klevebring, Daniel and Lindberg, Johan and Rockberg, Julia and Hilliges, Camilla and Hall, Per and Sandberg, Maria and Czene, Kamila},
  issn         = {1573-7217},
  keyword      = {Alleles,Breast Neoplasms,Exome,Female,High-Throughput Nucleotide Sequencing,Humans,Mutation,Neoplasm Metastasis,Prognosis,Registries,Journal Article},
  language     = {eng},
  number       = {2},
  pages        = {24--319},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {Exome sequencing of contralateral breast cancer identifies metastatic disease},
  url          = {http://dx.doi.org/10.1007/s10549-015-3403-6},
  volume       = {151},
  year         = {2015},
}