Whole Genome Analysis Informs Breast Cancer Response to Aromatase Inhibition

By M. Ellis, Li Ding, D. Shen, Jingqin R Luo, V. Suman, J. Wallis, B. V. Van Tine, J. Hoog, Reece J. Goiffon, Theodore Goldstein and 49 more. Nature, 2012

1,068 citations recorded by the source corpus.

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

Subfields: Cancer Research, Pathology and Forensic Medicine, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/947951c700b0a018e82be35c62520e274c7f618a

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Citations in the corpus

The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes (2016, positive): “The 173 genes sequenced include those that harboured mutations in at least 2 samples in 5 large-scale sequencing studies published in 2012 (refs 7–11) and also some targeted by homozygous deletions (HDs) we previously identiﬁed 3 .”
Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 (2013, background): “The genomic atlas of the disease [2] has emphasized its heterogeneity, and suggested that genomic studies may potentially inform treatment decisions such as the use of aromatase inhibitors [3, 4].”
Clonal Evolution in Breast Cancer Revealed by Single Nucleus Genome Sequencing (2014, background): “These data suggest that triple-negative breast cancers (TNBCs) may have increased clonal diversity and mutational evolution, but such inferences are difficult to make in bulk tissues 8,9 .”
Lessons from the cancer genome. (2013, neutral): “These included the MAP3K1 and MAP2K4 genes in breast cancer (encoding serine/threonine kinases involved in the P38JNK signaling pathway) (Banerji et al., 2012; Ellis et al., 2012; Stephens et al., 2012; CGAN, 2012), RAC1 in melanoma (a GTPase involved in the RAC/PAK-signaling module involved in foca”
Dynamics of genomic clones in breast cancer patient xenografts at single cell resolution (2014, neutral): “Cluster (n) 1 (85) 2 (15) 3 (9) 4 (6) 5 (6) 6 (5) 7 (4) 8 (2) 9 (2) 10 (2) b SA429”