Differential oestrogen receptor binding is associated with clinical outcome in breast cancer.

Paper of the Month: March, 2012

Nature. 2012 Jan 4;481(7381):389-93. doi: 10.1038/nature10730.

Ross-Innes CSStark RTeschendorff AEHolmes KAAli HRDunning MJBrown GDGojis OEllis IOGreen ARAli SChin SFPalmieri CCaldas C,Carroll JS.


Click here for Pubmed Abstract


Comments by Dr. Murray Gardner:

By genome-wide  chromatin immunoprecipitation  followed by  high- throughput  sequencing the authors have mapped the estrogen receptor (ER)  transcription factor in primary human breast cancers. They find great plasticity in ER binding mediated by the FOX A-1 transcription factor. Distinct ER binding patterns are associated with favorable or poor drug response and clinical outcome. Gene expression profiles were also predictive of response. In poor outcome patients specific genes such as the ERB2 oncogene were preferentially upregulated whereas in those with good outcome this oncogene was preferentially downregulated. Interestingly, the gene predictors were largely independent of histopathological features. The good and poor outcome gene predictors had no predictive value in ER negative tumors. Mapping of primary regulatory regions in primary tumors rather than secondary events such as gene expression profiles could lead to improved diagnostic, prognostic and treatment modalities.



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