The molecular diversity of Luminal A breast tumors

Giovanni Ciriello, Rileen Sinha, Katherine A. Hoadley, Anders S. Jacobsen, Boris Reva, Charles M. Perou, Chris Sander, Nikolaus Schultz

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Breast cancer is a collection of diseases with distinct molecular traits, prognosis, and therapeutic options. Luminal A breast cancer is the most heterogeneous, both molecularly and clinically. Using genomic data from over 1,000 Luminal A tumors from multiple studies, we analyzed the copy number and mutational landscape of this tumor subtype. This integrated analysis revealed four major subtypes defined by distinct copy-number and mutation profiles. We identified an atypical Luminal A subtype characterized by high genomic instability, TP53 mutations, and increased Aurora kinase signaling; these genomic alterations lead to a worse clinical prognosis. Aberrations of chromosomes 1, 8, and 16, together with PIK3CA, GATA3, AKT1, and MAP3K1 mutations drive the other subtypes. Finally, an unbiased pathway analysis revealed multiple rare, but mutually exclusive, alterations linked to loss of activity of co-repressor complexes N-Cor and SMRT. These rare alterations were the most prevalent in Luminal A tumors and may predict resistance to endocrine therapy. Our work provides for a further molecular stratification of Luminal A breast tumors, with potential direct clinical implications.

Original languageEnglish
Pages (from-to)409-420
Number of pages12
JournalBreast Cancer Research and Treatment
Volume141
Issue number3
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Breast cancer genomics
  • Luminal A breast cancer

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