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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
RECQL4 helicase has oncogenic potential in sporadic breast cancers
Journal of Pathology, Volume 238, No. 4, Year 2016
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Description
RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund-Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a 'safe guardian of the genome', our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors & Co-Authors
Agarwal, Devika
United Kingdom, Nottingham
Nottingham Trent University
Abdel-Fatah, Tarek M.A.
United Kingdom, Nottingham
Nottingham University Hospitals Nhs Trust
Moseley, Paul M.
United Kingdom, Nottingham
Nottingham University Hospitals Nhs Trust
Aleskandarany, Mohammed A.
United Kingdom, Nottingham
University of Nottingham
Green, Andew R.
United Kingdom, Nottingham
University of Nottingham
Ball, Graham Roy
United Kingdom, Nottingham
Nottingham Trent University
Rakha, Emad A.
United Kingdom, Nottingham
University of Nottingham
Chan, Stephen Y.T.
United Kingdom, Nottingham
Nottingham University Hospitals Nhs Trust
Ellis, Ian O.
United Kingdom, Nottingham
University of Nottingham
Wang, Lisa L.
United States, Houston
Texas Children's Cancer Center and Hematology Service
Balajee, Adáyabalam S.
United States, Oak Ridge
Oak Ridge Institute for Science and Education
Madhusudan, Srinivasan
United Kingdom, Nottingham
Nottingham University Hospitals Nhs Trust
Statistics
Citations: 37
Authors: 12
Affiliations: 7
Identifiers
Doi:
10.1002/path.4681
ISSN:
00223417
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health
Study Design
Cohort Study