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Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers.
Veeraraghavan, Jamunarani; Tan, Ying; Cao, Xi-Xi; Kim, Jin Ah; Wang, Xian; Chamness, Gary C; Maiti, Sourindra N; Cooper, Laurence J N; Edwards, Dean P; Contreras, Alejandro; Hilsenbeck, Susan G; Chang, Eric C; Schiff, Rachel; Wang, Xiao-Song.
Affiliation
  • Veeraraghavan J; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA [4].
  • Tan Y; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA [4].
  • Cao XX; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA [4].
  • Kim JA; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Wang X; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Chamness GC; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Maiti SN; Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Cooper LJ; Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Edwards DP; 1] Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA [2] Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Contreras A; Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Hilsenbeck SG; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Chang EC; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Schiff R; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA [4] Department of Molecular and Cellu
  • Wang XS; 1] Lester &Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA [2] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA [4] Department of Molecular and Cellu
Nat Commun ; 5: 4577, 2014 Aug 07.
Article in En | MEDLINE | ID: mdl-25099679
ABSTRACT
Characterizing the genetic alterations leading to the more aggressive forms of oestrogen receptor-positive (ER+) breast cancers is of critical significance in breast cancer management. Here we identify recurrent rearrangements between the oestrogen receptor gene ESR1 and its neighbour CCDC170, which are enriched in the more aggressive and endocrine-resistant luminal B tumours, through large-scale analyses of breast cancer transcriptome and copy number alterations. Further screening of 200 ER+ breast cancers identifies eight ESR1-CCDC170-positive tumours. These fusions encode amino-terminally truncated CCDC170 proteins (ΔCCDC170). When introduced into ER+ breast cancer cells, ΔCCDC170 leads to markedly increased cell motility and anchorage-independent growth, reduced endocrine sensitivity and enhanced xenograft tumour formation. Mechanistic studies suggest that ΔCCDC170 engages Gab1 signalosome to potentiate growth factor signalling and enhance cell motility. Together, this study identifies neoplastic ESR1-CCDC170 fusions in a more aggressive subset of ER+ breast cancer, which suggests a new concept of ER pathobiology in breast cancer.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Gene Rearrangement / Carrier Proteins / Gene Expression Regulation, Neoplastic / Estrogen Receptor alpha Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2014 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Gene Rearrangement / Carrier Proteins / Gene Expression Regulation, Neoplastic / Estrogen Receptor alpha Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2014 Document type: Article