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Br J Cancer. 2013 Nov 12;109(10):2724-34. doi: 10.1038/bjc.2013.612. Epub 2013 Oct 8.

MicroRNA-based molecular classification of non-BRCA1/2 hereditary breast tumours.

Author information

1
Human Genetics Group, Spanish National Cancer Research Centre (CNIO) y Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.

Abstract

BACKGROUND:

Hereditary breast cancer comprises 5-10% of all breast cancers. Mutations in two high-risk susceptibility genes, BRCA1 and BRCA2, along with rare intermediate-risk genes and common low-penetrance alleles identified, altogether explain no more than 45% of the high-risk breast cancer families, although the majority of cases are unaccounted for and are designated as BRCAX tumours. Micro RNAs have called great attention for classification of different cancer types and have been implicated in a range of important biological processes and are deregulated in cancer pathogenesis.

METHODS:

Here we have performed an exploratory hypothesis-generating study of miRNA expression profiles in a large series of 66 primary hereditary breast tumours by microarray analysis.

RESULTS:

Unsupervised clustering analysis of miRNA molecular profiles revealed distinct subgroups of BRCAX tumours, 'normal-like' BRCAX-A, 'proliferative' BRCAX-B, 'BRCA1/2-like' BRCAX-C and 'undefined' BRCAX-D subgroup. These findings introduce a new insight in the biology of hereditary breast cancer, defining specific BRCAX subgroups, which could help in the search for novel susceptibility pathways in hereditary breast cancer.

CONCLUSION:

Our data demonstrate that BRCAX hereditary breast tumours can be sub-classified into four previously unknown homogenous groups characterised by specific miRNA expression signatures and histopathological features.

PMID:
24104964
PMCID:
PMC3833208
DOI:
10.1038/bjc.2013.612
[Indexed for MEDLINE]
Free PMC Article

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