Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/101754
Title: Comprehensive molecular portraits of human breast tumours
Author: Prat Aparicio, Aleix
Keywords: Càncer de mama
Genòmica
Expressió gènica
Oncologia
Breast cancer
Genomics
Gene expression
Oncology
Issue Date: 23-Sep-2012
Publisher: Nature Publishing Group
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.
Note: Versió postprint del document publicat a: http://dx.doi.org/10.1038/nature11412
It is part of: Nature, 2012, vol. 490, num. 7418, p. 61-70
Related resource: http://dx.doi.org/10.1038/nature11412
URI: http://hdl.handle.net/2445/101754
ISSN: 0028-0836
Appears in Collections:Articles publicats en revistes (Medicina)

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