Type

Journal Article

Authors

Shiaw-Yih Lin
Gordon B Mills
Samir Hanash
Bryan Hennessy
Ju-Seog Lee
Ruozhen Hu
Stefan Siwko
Qianxing Mo
Yang Peng
Soo Mi Kim
and 5 others

Subjects

Biochemistry

Topics
network analysis cancer cells drug discovery dna damage genome dna repair functional analysis dna profiling

Genome-wide transcriptome profiling of homologous recombination DNA repair. (2014)

Abstract Homologous recombination (HR) repair deficiency predisposes to cancer development, but also sensitizes cancer cells to DNA damage-inducing therapeutics. Here we identify an HR defect (HRD) gene signature that can be used to functionally assess HR repair status without interrogating individual genetic alterations in cells. By using this HRD gene signature as a functional network analysis tool, we discover that simultaneous loss of two major tumour suppressors BRCA1 and PTEN extensively rewire the HR repair-deficient phenotype, which is found in cells with defects in either BRCA1 or PTEN alone. Moreover, the HRD gene signature serves as an effective drug discovery platform to identify agents targeting HR repair as potential chemo/radio sensitizers. More importantly, this HRD gene signature is able to predict clinical outcomes across multiple cancer lineages. Our findings, therefore, provide a molecular profile of HR repair to assess its status at a functional network level, which can provide both biological insights and have clinical implications in cancer.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Shiaw-Yih Lin, Gordon B Mills, Samir Hanash, Bryan Hennessy, Ju-Seog Lee, Ruozhen Hu, Stefan Siwko, Qianxing Mo, Yang Peng, Soo Mi Kim and 5 others

Experts in our system

1
Gordon B Mills
Royal College of Surgeons in Ireland
Total Publications: 4
 
2
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33