Whole-genome analysis informs breast cancer response to aromatase inhibition

Matthew J. Ellis, Li Ding, Dong Shen, Jingqin Luo, Vera Jean Suman, John W. Wallis, Brian A. Van Tine, Jeremy Hoog, Reece J. Goiffon, Theodore C. Goldstein, Sam Ng, Li Lin, Robert Crowder, Jacqueline Snider, Karla Ballman, Jason Weber, Ken Chen, Daniel C. Koboldt, Cyriac Kandoth, William S. Schierding & 39 others Joshua F. McMichael, Christopher A. Miller, Charles Lu, Christopher C. Harris, Michael D. McLellan, Michael C. Wendl, Katherine Deschryver, D. Craig Allred, Laura Esserman, Gary Unzeitig, Julie Margenthaler, G. V. Babiera, P. Kelly Marcom, J. M. Guenther, Marilyn Leitch, Kelly Hunt, John Olson, Yu Tao, Christopher A. Maher, Lucinda L. Fulton, Robert S. Fulton, Michelle Harrison, Ben Oberkfell, Feiyu Du, Ryan Demeter, Tammi L. Vickery, Adnan Elhammali, Helen Piwnica-Worms, Sandra McDonald, Mark Watson, David J. Dooling, David Ota, Li Wei Chang, Ron Bose, Timothy J. Ley, David Piwnica-Worms, Joshua M. Stuart, Richard K. Wilson, Elaine R. Mardis

Research output: Contribution to journalArticle

653 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalNature
Volume486
Issue number7403
DOIs
StatePublished - Jun 21 2012

Fingerprint

Aromatase
Aromatase Inhibitors
Genome
Breast Neoplasms
Estrogen Receptors
Mutation
High-Throughput Nucleotide Sequencing
Genes
Neoplasms
Histology
Clinical Trials
Phenotype
Biopsy
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

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

Whole-genome analysis informs breast cancer response to aromatase inhibition. / Ellis, Matthew J.; Ding, Li; Shen, Dong; Luo, Jingqin; Suman, Vera Jean; Wallis, John W.; Van Tine, Brian A.; Hoog, Jeremy; Goiffon, Reece J.; Goldstein, Theodore C.; Ng, Sam; Lin, Li; Crowder, Robert; Snider, Jacqueline; Ballman, Karla; Weber, Jason; Chen, Ken; Koboldt, Daniel C.; Kandoth, Cyriac; Schierding, William S.; McMichael, Joshua F.; Miller, Christopher A.; Lu, Charles; Harris, Christopher C.; McLellan, Michael D.; Wendl, Michael C.; Deschryver, Katherine; Allred, D. Craig; Esserman, Laura; Unzeitig, Gary; Margenthaler, Julie; Babiera, G. V.; Marcom, P. Kelly; Guenther, J. M.; Leitch, Marilyn; Hunt, Kelly; Olson, John; Tao, Yu; Maher, Christopher A.; Fulton, Lucinda L.; Fulton, Robert S.; Harrison, Michelle; Oberkfell, Ben; Du, Feiyu; Demeter, Ryan; Vickery, Tammi L.; Elhammali, Adnan; Piwnica-Worms, Helen; McDonald, Sandra; Watson, Mark; Dooling, David J.; Ota, David; Chang, Li Wei; Bose, Ron; Ley, Timothy J.; Piwnica-Worms, David; Stuart, Joshua M.; Wilson, Richard K.; Mardis, Elaine R.

In: Nature, Vol. 486, No. 7403, 21.06.2012, p. 353-360.

Research output: Contribution to journalArticle

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, LW, Bose, R, Ley, TJ, Piwnica-Worms, D, Stuart, JM, Wilson, RK & Mardis, ER 2012, 'Whole-genome analysis informs breast cancer response to aromatase inhibition', Nature, vol. 486, no. 7403, pp. 353-360. 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 21;486(7403):353-360. https://doi.org/10.1038/nature11143
Ellis, Matthew J. ; Ding, Li ; Shen, Dong ; Luo, Jingqin ; Suman, Vera Jean ; Wallis, John W. ; Van Tine, Brian A. ; Hoog, Jeremy ; Goiffon, Reece J. ; Goldstein, Theodore C. ; Ng, Sam ; Lin, Li ; Crowder, Robert ; Snider, Jacqueline ; Ballman, Karla ; Weber, Jason ; Chen, Ken ; Koboldt, Daniel C. ; Kandoth, Cyriac ; Schierding, William S. ; McMichael, Joshua F. ; Miller, Christopher A. ; Lu, Charles ; Harris, Christopher C. ; McLellan, Michael D. ; Wendl, Michael C. ; Deschryver, Katherine ; Allred, D. Craig ; Esserman, Laura ; Unzeitig, Gary ; Margenthaler, Julie ; Babiera, G. V. ; Marcom, P. Kelly ; Guenther, J. M. ; Leitch, Marilyn ; Hunt, Kelly ; Olson, John ; Tao, Yu ; Maher, Christopher A. ; Fulton, Lucinda L. ; Fulton, Robert S. ; Harrison, Michelle ; Oberkfell, Ben ; Du, Feiyu ; Demeter, Ryan ; Vickery, Tammi L. ; Elhammali, Adnan ; Piwnica-Worms, Helen ; McDonald, Sandra ; Watson, Mark ; Dooling, David J. ; Ota, David ; Chang, Li Wei ; Bose, Ron ; Ley, Timothy J. ; Piwnica-Worms, David ; Stuart, Joshua M. ; Wilson, Richard K. ; Mardis, Elaine R. / Whole-genome analysis informs breast cancer response to aromatase inhibition. In: Nature. 2012 ; Vol. 486, No. 7403. pp. 353-360.
@article{50408455ab344ba0931b08b1b309b5a4,
title = "Whole-genome analysis informs breast cancer response to aromatase inhibition",
abstract = "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.",
author = "Ellis, {Matthew J.} and Li Ding and Dong Shen and Jingqin Luo and Suman, {Vera Jean} and Wallis, {John W.} and {Van Tine}, {Brian A.} and Jeremy Hoog and Goiffon, {Reece J.} and Goldstein, {Theodore C.} and Sam Ng and Li Lin and Robert Crowder and Jacqueline Snider and Karla Ballman and Jason Weber and Ken Chen and Koboldt, {Daniel C.} and Cyriac Kandoth and Schierding, {William S.} and McMichael, {Joshua F.} and Miller, {Christopher A.} and Charles Lu and Harris, {Christopher C.} and McLellan, {Michael D.} and Wendl, {Michael C.} and Katherine Deschryver and Allred, {D. Craig} and Laura Esserman and Gary Unzeitig and Julie Margenthaler and Babiera, {G. V.} and Marcom, {P. Kelly} and Guenther, {J. M.} and Marilyn Leitch and Kelly Hunt and John Olson and Yu Tao and Maher, {Christopher A.} and Fulton, {Lucinda L.} and Fulton, {Robert S.} and Michelle Harrison and Ben Oberkfell and Feiyu Du and Ryan Demeter and Vickery, {Tammi L.} and Adnan Elhammali and Helen Piwnica-Worms and Sandra McDonald and Mark Watson and Dooling, {David J.} and David Ota and Chang, {Li Wei} and Ron Bose and Ley, {Timothy J.} and David Piwnica-Worms and Stuart, {Joshua M.} and Wilson, {Richard K.} and Mardis, {Elaine R.}",
year = "2012",
month = "6",
day = "21",
doi = "10.1038/nature11143",
language = "English (US)",
volume = "486",
pages = "353--360",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7403",

}

TY - JOUR

T1 - Whole-genome analysis informs breast cancer response to aromatase inhibition

AU - Ellis, Matthew J.

AU - Ding, Li

AU - Shen, Dong

AU - Luo, Jingqin

AU - Suman, Vera Jean

AU - Wallis, John W.

AU - Van Tine, Brian A.

AU - Hoog, Jeremy

AU - Goiffon, Reece J.

AU - Goldstein, Theodore C.

AU - Ng, Sam

AU - Lin, Li

AU - Crowder, Robert

AU - Snider, Jacqueline

AU - Ballman, Karla

AU - Weber, Jason

AU - Chen, Ken

AU - Koboldt, Daniel C.

AU - Kandoth, Cyriac

AU - Schierding, William S.

AU - McMichael, Joshua F.

AU - Miller, Christopher A.

AU - Lu, Charles

AU - Harris, Christopher C.

AU - McLellan, Michael D.

AU - Wendl, Michael C.

AU - Deschryver, Katherine

AU - Allred, D. Craig

AU - Esserman, Laura

AU - Unzeitig, Gary

AU - Margenthaler, Julie

AU - Babiera, G. V.

AU - Marcom, P. Kelly

AU - Guenther, J. M.

AU - Leitch, Marilyn

AU - Hunt, Kelly

AU - Olson, John

AU - Tao, Yu

AU - Maher, Christopher A.

AU - Fulton, Lucinda L.

AU - Fulton, Robert S.

AU - Harrison, Michelle

AU - Oberkfell, Ben

AU - Du, Feiyu

AU - Demeter, Ryan

AU - Vickery, Tammi L.

AU - Elhammali, Adnan

AU - Piwnica-Worms, Helen

AU - McDonald, Sandra

AU - Watson, Mark

AU - Dooling, David J.

AU - Ota, David

AU - Chang, Li Wei

AU - Bose, Ron

AU - Ley, Timothy J.

AU - Piwnica-Worms, David

AU - Stuart, Joshua M.

AU - Wilson, Richard K.

AU - Mardis, Elaine R.

PY - 2012/6/21

Y1 - 2012/6/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84862584058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862584058&partnerID=8YFLogxK

U2 - 10.1038/nature11143

DO - 10.1038/nature11143

M3 - Article

VL - 486

SP - 353

EP - 360

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7403

ER -