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MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours

Green, Andrew R.; Aleskandarany, Mohammed A.; Agarwal, Devika; Elsheikh, Somaia; Nolan, Christopher C.; Diez-Rodriguez, Maria; Macmillan, R. Douglas; Ball, Graham R.; Caldas, Carlos; Madhusudan, Srinivasan; Ellis, Ian O.; Rakha, Emad A.

Authors

Mohammed A. Aleskandarany

Devika Agarwal

Somaia Elsheikh

Christopher C. Nolan

Maria Diez-Rodriguez

R. Douglas Macmillan

Graham R. Ball

Carlos Caldas

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



Abstract

Background:

MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs.

Methods:

We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients’ outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunuohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes.

Results:

High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P

Journal Article Type Article
Publication Date 2016-04
Journal British Journal of Cancer
Print ISSN 0007-0920
Electronic ISSN 1532-1827
Publisher Cancer Research UK
Peer Reviewed Peer Reviewed
Volume 114
Issue 8
Pages 917-928
APA6 Citation Green, A. R., Aleskandarany, M. A., Agarwal, D., Elsheikh, S., Nolan, C. C., Diez-Rodriguez, M., …Rakha, E. A. (2016). MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours. British Journal of Cancer, 114(8), 917-928. doi:10.1038/bjc.2016.46
DOI https://doi.org/10.1038/bjc.2016.46
Publisher URL https://www.nature.com/articles/bjc201646

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