| Literature DB >> 30205045 |
Pedram Razavi1, Matthew T Chang2, Guotai Xu3, Chaitanya Bandlamudi4, Dara S Ross5, Neil Vasan1, Yanyan Cai5, Craig M Bielski4, Mark T A Donoghue4, Philip Jonsson2, Alexander Penson2, Ronglai Shen6, Fresia Pareja5, Ritika Kundra4, Sumit Middha5, Michael L Cheng7, Ahmet Zehir5, Cyriac Kandoth4, Ruchi Patel4, Kety Huberman4, Lillian M Smyth7, Komal Jhaveri7, Shanu Modi7, Tiffany A Traina7, Chau Dang7, Wen Zhang7, Britta Weigelt5, Bob T Li7, Marc Ladanyi8, David M Hyman7, Nikolaus Schultz9, Mark E Robson7, Clifford Hudis7, Edi Brogi5, Agnes Viale4, Larry Norton7, Maura N Dickler7, Michael F Berger10, Christine A Iacobuzio-Donahue8, Sarat Chandarlapaty1, Maurizio Scaltriti8, Jorge S Reis-Filho8, David B Solit11, Barry S Taylor12, José Baselga13.
Abstract
We integrated the genomic sequencing of 1,918 breast cancers, including 1,501 hormone receptor-positive tumors, with detailed clinical information and treatment outcomes. In 692 tumors previously exposed to hormonal therapy, we identified an increased number of alterations in genes involved in the mitogen-activated protein kinase (MAPK) pathway and in the estrogen receptor transcriptional machinery. Activating ERBB2 mutations and NF1 loss-of-function mutations were more than twice as common in endocrine resistant tumors. Alterations in other MAPK pathway genes (EGFR, KRAS, among others) and estrogen receptor transcriptional regulators (MYC, CTCF, FOXA1, and TBX3) were also enriched. Altogether, these alterations were present in 22% of tumors, mutually exclusive with ESR1 mutations, and associated with a shorter duration of response to subsequent hormonal therapies.Entities:
Keywords: breast cancer; cancer genomics; endocrine resistance; integrative genomics analysis; metastasis
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Year: 2018 PMID： 30205045 PMCID： PMC6327853 DOI： 10.1016/j.ccell.2018.08.008
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743