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Whole-genome analysis informs breast cancer response to aromatase inhibition.

Publication ,  Journal Article
Ellis, MJ; Ding, L; Shen, D; Luo, J; Suman, VJ; Wallis, JW; Van Tine, BA; Hoog, J; Goiffon, RJ; Goldstein, TC; Ng, S; Lin, L; Crowder, R ...
Published in: Nature
June 10, 2012

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

June 10, 2012

Volume

486

Issue

7403

Start / End Page

353 / 360

Location

England

Related Subject Headings

  • Triazoles
  • Treatment Outcome
  • Receptors, Estrogen
  • Nitriles
  • Mutation
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase 4
  • Letrozole
  • Humans
  • Genome, Human
 

Citation

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Chicago
ICMJE
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Ellis, M. J., Ding, L., Shen, D., Luo, J., Suman, V. J., Wallis, J. W., … Mardis, E. R. (2012). Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature, 486(7403), 353–360. https://doi.org/10.1038/nature11143
Ellis, Matthew J., Li Ding, Dong Shen, Jingqin Luo, Vera J. Suman, John W. Wallis, Brian A. Van Tine, et al. “Whole-genome analysis informs breast cancer response to aromatase inhibition.Nature 486, no. 7403 (June 10, 2012): 353–60. https://doi.org/10.1038/nature11143.
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012 Jun 10;486(7403):353–60.
Ellis, Matthew J., et al. “Whole-genome analysis informs breast cancer response to aromatase inhibition.Nature, vol. 486, no. 7403, June 2012, pp. 353–60. Pubmed, doi:10.1038/nature11143.
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding WS, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Leitch M, Hunt K, Olson J, Tao Y, Maher CA, Fulton LL, Fulton RS, Harrison M, Oberkfell B, Du F, Demeter R, Vickery TL, Elhammali A, Piwnica-Worms H, McDonald S, Watson M, Dooling DJ, Ota D, Chang L-W, Bose R, Ley TJ, Piwnica-Worms D, Stuart JM, Wilson RK, Mardis ER. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012 Jun 10;486(7403):353–360.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

June 10, 2012

Volume

486

Issue

7403

Start / End Page

353 / 360

Location

England

Related Subject Headings

  • Triazoles
  • Treatment Outcome
  • Receptors, Estrogen
  • Nitriles
  • Mutation
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase 4
  • Letrozole
  • Humans
  • Genome, Human