Abstract
Homologous recombination (HR) is the primary pathway for repairing double-strand DNA breaks implicating in the development of cancer. RNAi-based knockdowns of BRCA1 and RAD51 in this pathway have been performed to investigate the resulting transcriptomic profiles. Here we propose a computational framework to utilize these profiles to calculate a score, named RNA-Interference derived Proliferation Score (RIPS), which reflects cell proliferation ability in individual breast tumors. RIPS is predictive of breast cancer classes, prognosis, genome instability, and neoadjuvant chemosensitivity. This framework directly translates the readout of knockdown experiments into potential clinical applications and generates a robust biomarker in breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0363-3) contains supplementary material, which is available to authorized users.
Highlights
Homologous recombination (HR) is the primary pathway for repairing double-strand DNA breaks (DSBs) and is highly conserved in eukaryotic organisms [1, 2]
We proposed a novel computational framework to investigate the similarity between the gene expression profiles derived from RNA interference (RNAi) experiments and breast tumors gene expression profiles
By applying the RNA-Interference derived Proliferation Score (RIPS), we were able to discriminate with fairly high accuracy breast tumors containing germline BRCA1 or BRCA2 mutations from those that occurred sporadically
Summary
Homologous recombination (HR) is the primary pathway for repairing double-strand DNA breaks (DSBs) and is highly conserved in eukaryotic organisms [1, 2]. BRCA1 and BRCA2, the most well-studied genes in this pathway [3, 4], participate in DNA repair either as essential proteins themselves or regulate other proteins in the HR pathway to facilitate repair of damaged DNA or apoptosis if DNA cannot be repaired [5]. BRCA1 and BRCA2 interact with RAD51 to form complexes that initiate and facilitate homologous recombination [6,7,8,9]. RAD51 catalyzes the key reactions in the HR pathway, including homology search and DNA strand invasion [1]. Mutation or deregulation of genes in the HR pathway has been implicated in the development of many cancer subtypes including breast cancer [10]. Mutations in BRCA1 and BRCA2 have long been known to confer cancer susceptibility [11] and women
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
