Whole-genome analysis informs breast cancer response to aromatase inhibition

被引：847

作者：

Ellis, Matthew J. ^{[1
,2
,3
]}

Ding, Li ^{[4
,5
]}

Shen, Dong ^{[4
,5
]}

Luo, Jingqin ^{[3
,6
]}

Suman, Vera J. ^{[7
]}

Wallis, John W. ^{[4
,5
]}

Van Tine, Brian A. ^{[1
]}

Hoog, Jeremy ^{[1
]}

Goiffon, Reece J. ^{[8
,9
,10
]}

Goldstein, Theodore C. ^{[11
]}

Ng, Sam ^{[11
]}

Lin, Li ^{[1
]}

Crowder, Robert ^{[1
]}

Snider, Jacqueline ^{[1
]}

Ballman, Karla ^{[7
]}

Weber, Jason ^{[1
,8
,12
]}

Chen, Ken ^{[13
]}

Koboldt, Daniel C. ^{[4
,5
]}

Kandoth, Cyriac ^{[4
,5
]}

Schierding, William S. ^{[4
,5
]}

McMichael, Joshua F. ^{[4
,5
]}

Miller, Christopher A. ^{[4
,5
]}

Lu, Charles ^{[4
,5
]}

Harris, Christopher C. ^{[4
,5
]}

McLellan, Michael D. ^{[4
,5
]}

Wendl, Michael C. ^{[4
,5
]}

DeSchryver, Katherine ^{[1
]}

Allred, D. Craig ^{[3
,14
]}

Esserman, Laura ^{[15
]}

Unzeitig, Gary ^{[16
]}

Margenthaler, Julie ^{[2
]}

Babiera, G. V. ^{[13
]}

Marcom, P. Kelly ^{[17
]}

Guenther, J. M. ^{[18
]}

Leitch, Marilyn ^{[19
]}

Hunt, Kelly ^{[13
]}

Olson, John ^{[17
]}

Tao, Yu ^{[6
]}

Maher, Christopher A. ^{[1
,4
]}

Fulton, Lucinda L. ^{[4
,5
]}

Fulton, Robert S. ^{[4
,5
]}

Harrison, Michelle ^{[4
,5
]}

Oberkfell, Ben ^{[4
,5
]}

Du, Feiyu ^{[4
,5
]}

Demeter, Ryan ^{[4
,5
]}

Vickery, Tammi L. ^{[4
,5
]}

Elhammali, Adnan ^{[8
,9
,10
]}

Piwnica-Worms, Helen ^{[8
,20
]}

McDonald, Sandra ^{[2
,21
]}

Watson, Mark ^{[6
,14
,21
]}

机构：

[1] Washington Univ, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA

[2] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA

[3] Washington Univ, Breast Canc Program, St Louis, MO 63110 USA

[4] Washington Univ, Genome Inst, St Louis, MO 63108 USA

[5] Washington Univ, Dept Genet, St Louis, MO 63108 USA

[6] Washington Univ, Div Biostat, St Louis, MO 63110 USA

[7] Mayo Clin, ACOSOG Stat Ctr, Rochester, MN 55905 USA

[8] Washington Univ, BRIGHT Inst, Sch Med, St Louis, MO 63110 USA

[9] Washington Univ, Mol Imaging Ctr, St Louis, MO 63110 USA

[10] Washington Univ, Malinckrodt Inst Radiol, St Louis, MO 63110 USA

[11] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[12] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63110 USA

[13] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[14] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA

[15] Univ Calif San Francisco, Helen Diller Canc Ctr, San Francisco, CA 94143 USA

[16] Doctors Hosp Laredo, Laredo, TX 78045 USA

[17] Duke Univ, Ctr Canc, Durham, NC 27705 USA

[18] Good Samaritan Hosp, Cincinnati, OH 45406 USA

[19] Univ Texas SW, Simmons Canc Ctr, Dallas, TX 75390 USA

[20] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[21] Washington Univ, ACOSOG Cent Specimen Bank, St Louis, MO 63110 USA

[22] Duke Univ, ACOSOG Operat Ctr, Durham, NC 27705 USA

[23] Washington Univ, Dept Dev Biol, St Louis, MO 63110 USA

来源：

NATURE | 2012年 / 486卷 / 7403期

基金：

美国国家科学基金会;

关键词：

MYELOID-LEUKEMIA GENOME; CELL LUNG-CANCER; ENDOCRINE THERAPY; SUPPRESSOR GENE; MUTATION; PATHWAY; PHOSPHORYLATION; MECHANISMS; CARCINOMA; OUTCOMES;

D O I：

10.1038/nature11143

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：353 / 360

页数：8

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