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Access through your institution Buy or subscribe ER-positive breast cancer is known to be heterogenous, and this is reflected in variable patient prognosis and response to treatment. To
glean insight into this complexity, the authors took advantage of an ongoing clinical trial in which aromatase inhibitors were used before subsequent surgical intervention. In total, over 70
whole genomes and exomes were sequenced, and selected findings were followed up in additional cases. The authors identified 18 frequently mutated genes, including known breast cancer genes
and known cancer genes that had not previously been linked to breast cancer, as well as genes that had not previously been implicated in cancer. Intriguingly, they identified many genes that
had previously been implicated in haematological cancers; the authors suggest that, similarly to those cancers, breast cancer might be a stem cell disorder. If it is true, this has
implications for our understanding of breast cancer evolution and could explain why the prognosis of ER-positive tumours is so variable. Among the frequently mutated genes was MAP3K1, a
serine/threonine kinase that activates the ERK and JNK kinase pathways. Mutations in this locus were found predominantly in the luminal A subtype of ER-positive cancers but also in those
that proliferated less aggressively. By contrast, mutations in _TP53_ (which encodes p53) were found in luminal B subtype and those that proliferated more aggressively. Aggressive
proliferation despite aromatase inhibitor therapy can indicate poor prognosis, and thus MAP3K1 might therefore be a useful marker of sensitivity to aromatase inhibitor treatment, whereas
_TP53_ mutations might indicate a likely lack of response. The authors also found some evidence that mutations in _GATA3_ might also be indicative of a response to aromatase inhibitor. This
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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL RESEARCH PAPER * Ellis, M. J. et
al. Whole-genome analysis informs breast cancer response to aromatase inhibition. _Nature_ 10 June 2012 (doi:10.1038/nature11143) Article CAS Google Scholar FURTHER READING * Meyerson,
M., Gabriel, S. & Getz, G. Advances in understanding cancer genomes through second-generation sequencing. _Nature Rev. Genet._ 11, 685–695 (2010) Article CAS Google Scholar Download
references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Senior Editor, Nature, Magdalena Skipper Authors * Magdalena Skipper View author publications You can also search for this author
inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Skipper, M. Indicators for drug response from sequencing. _Nat Rev Genet_ 13, 520
(2012). https://doi.org/10.1038/nrg3285 Download citation * Published: 19 June 2012 * Issue Date: August 2012 * DOI: https://doi.org/10.1038/nrg3285 SHARE THIS ARTICLE Anyone you share the
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