Paper of the Month: March, 2012
Nature. 2012 Jan 4;481(7381):389-93. doi: 10.1038/nature10730.
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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