The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes
By Bernard Pereira, S. Chin, O. Rueda, H. Vollan, E. Provenzano, H. Bardwell, Michelle Pugh, Linda Jones, R. Russell, Stephen John Sammut and 24 more. Nature Communications, 2016
1,612 citations recorded by the source corpus.
The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies. Much effort has recently been devoted to understanding the genomics of breast cancer. In this study, the authors integrate somatic mutation data with previously published copy number aberration and gene expression information for nearly 2,500 breast cancer samples.
Subfields: Cancer Research, Genetics, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/01316791505a4d0d31496d7993ec8acc128dfb09
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Citations in the corpus
- A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. (2018, neutral): “CNAs generally affect a large portion of the BC genome and include driver as well as passenger events (Pereira et al., 2016; Zack et al., 2013).”
- The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers (2018, background): “Broad-based genomic characterization of breast cancer has largely established the landscape of inherited and somatic genomic alterations that typify each of these classes of primary disease (Banerji et al., 2012; Cancer Genome Atlas, 2012; Ciriello et al., 2015; Ellis et al., 2012; Nik-Zainal et al.”