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Recurrent and functional regulatory mutations in breast cancer.
Rheinbay, Esther; Parasuraman, Prasanna; Grimsby, Jonna; Tiao, Grace; Engreitz, Jesse M; Kim, Jaegil; Lawrence, Michael S; Taylor-Weiner, Amaro; Rodriguez-Cuevas, Sergio; Rosenberg, Mara; Hess, Julian; Stewart, Chip; Maruvka, Yosef E; Stojanov, Petar; Cortes, Maria L; Seepo, Sara; Cibulskis, Carrie; Tracy, Adam; Pugh, Trevor J; Lee, Jesse; Zheng, Zongli; Ellisen, Leif W; Iafrate, A John; Boehm, Jesse S; Gabriel, Stacey B; Meyerson, Matthew; Golub, Todd R; Baselga, Jose; Hidalgo-Miranda, Alfredo; Shioda, Toshi; Bernards, Andre; Lander, Eric S; Getz, Gad.
Afiliación
  • Rheinbay E; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Parasuraman P; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Grimsby J; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Tiao G; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Engreitz JM; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Kim J; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Lawrence MS; Division of Health Sciences and Technology, MIT, Cambridge, Massachusetts 02139, USA.
  • Taylor-Weiner A; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Rodriguez-Cuevas S; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Rosenberg M; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Hess J; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Stewart C; Instituto de Enfermedades de la Mama FUCAM, A.C., Mexico City 04980, Mexico.
  • Maruvka YE; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Stojanov P; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Cortes ML; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Seepo S; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Cibulskis C; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Tracy A; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Pugh TJ; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Lee J; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Zheng Z; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Ellisen LW; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Iafrate AJ; Princess Margaret Cancer Centre, University Health Network and the Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
  • Boehm JS; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Gabriel SB; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Meyerson M; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Golub TR; Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Baselga J; Massachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
  • Hidalgo-Miranda A; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Shioda T; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Bernards A; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
  • Lander ES; Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Getz G; Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Nature ; 547(7661): 55-60, 2017 07 06.
Article en En | MEDLINE | ID: mdl-28658208
ABSTRACT
Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Regulación Neoplásica de la Expresión Génica / Regiones Promotoras Genéticas / Mutación Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nature Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Regulación Neoplásica de la Expresión Génica / Regiones Promotoras Genéticas / Mutación Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nature Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos