Your browser doesn't support javascript.
loading
BRAF fusions identified in melanomas have variable treatment responses and phenotypes.
Turner, Jacqueline A; Bemis, Judson G T; Bagby, Stacey M; Capasso, Anna; Yacob, Betelehem W; Chimed, Tugs-Saikhan; Van Gulick, Robert; Lee, Hannah; Tobin, Richard; Tentler, John J; Pitts, Todd; McCarter, Martin; Robinson, William A; Couts, Kasey L.
Afiliação
  • Turner JA; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Bemis JGT; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Bagby SM; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Capasso A; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Yacob BW; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Chimed TS; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Van Gulick R; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Lee H; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Tobin R; Department of Medicine, Internal Medicine Residency Training Program, University of Colorado Denver, Aurora, CO, USA.
  • Tentler JJ; Division Surgical Oncology, Department of Surgery, University of Colorado Denver, Aurora, CO, USA.
  • Pitts T; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • McCarter M; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
  • Robinson WA; Division Surgical Oncology, Department of Surgery, University of Colorado Denver, Aurora, CO, USA.
  • Couts KL; Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
Oncogene ; 38(8): 1296-1308, 2019 02.
Article em En | MEDLINE | ID: mdl-30254212
ABSTRACT
Oncogenic BRAF fusions have emerged as an alternate mechanism for BRAF activation in melanomas and other cancers. A number of BRAF fusions with different 5' gene partners and BRAF exon breakpoints have been described, but the effects of different partners and breakpoints on cancer phenotypes and treatment responses has not been well characterized. Targeted RNA sequencing was used to screen 60 melanoma patient-derived xenograft (PDX) models for BRAF fusions. We identified three unique BRAF fusions, including a novel SEPT3-BRAF fusion, occurring in four tumors (4/60, 6.7%), all of which were "pan-negative" (lacking other common mutations) (4/18, 22.2%). The BRAF fusion PDX models showed variable growth rates and responses to MAPK inhibitors in vivo. Overexpression of BRAF fusions identified in our study, as well as other BRAF fusions previously identified in melanomas, resulted in a high degree of variability in 2D proliferation and 3D invasion between the different fusions. While exogenously expressed BRAF fusions all responded to MAPK inhibition in vitro, we observed potential differences in signaling and feedback mechanisms. In summary, BRAF fusions are actionable therapeutic targets, however there are significant differences in phenotypes, treatment responses, and signaling which may be clinically relevant.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Fusão Oncogênica / Proteínas Proto-Oncogênicas B-raf / Septinas / Melanoma Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Fusão Oncogênica / Proteínas Proto-Oncogênicas B-raf / Septinas / Melanoma Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos