UMMS Affiliation

Department of Molecular, Cell and Cancer Biology

Publication Date

11-16-2017

Document Type

Article

Disciplines

Cancer Biology | Computational Biology | Genetic Phenomena | Molecular Genetics | Neoplasms

Abstract

BRCAness has important implications in the management and treatment of patients with breast and ovarian cancer. In this study, we propose a computational framework to measure the BRCAness of breast and ovarian tumor samples based on their gene expression profiles. We define a characteristic profile for BRCAness by comparing gene expression differences between BRCA1/2 mutant familial tumors and sporadic breast cancer tumors while adjusting for relevant clinical factors. With this BRCAness profile, our framework calculates sample-specific BRCA scores, which indicates homologous recombination (HR)-mediated DNA repair pathway activity of samples. We found that in sporadic breast cancer high BRCAness score is associated with aberrant copy number of HR genes rather than somatic mutation and other genomic features. Moreover, we observed significant correlations of BRCA score with genome instability and neoadjuvant chemotherapy. More importantly, BRCA score provides significant prognostic value in both breast and ovarian cancers after considering established clinical variables. In summary, the inferred BRCAness from our framework can be used as a robust biomarker for the prediction of prognosis and treatment response in breast and ovarian cancers.

Keywords

Breast cancer, Cancer epigenetics, Computational models

Rights and Permissions

Copyright © The Author(s) 2017. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41598-017-16138-2

Source

Sci Rep. 2017 Nov 16;7(1):15742. doi: 10.1038/s41598-017-16138-2. Link to article on publisher's site

Journal/Book/Conference Title

Scientific reports

Related Resources

Link to Article in PubMed

PubMed ID

29146938

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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