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Altered regulation of DPF3, a member of the SWI/SNF complexes, underlies the 14q24 renal cancer susceptibility locus.
Colli, Leandro M; Jessop, Lea; Myers, Timothy A; Camp, Sabrina Y; Machiela, Mitchell J; Choi, Jiyeon; Cunha, Renato; Onabajo, Olusegun; Mills, Grace C; Schmid, Virginia; Brodie, Seth A; Delattre, Olivier; Mole, David R; Purdue, Mark P; Yu, Kai; Brown, Kevin M; Chanock, Stephen J.
Afiliación
  • Colli LM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA; Department of Medical Imaging, Hematology, and Oncology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14040-900, Brazil.
  • Jessop L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Myers TA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Camp SY; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Machiela MJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Choi J; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Cunha R; Department of Medical Imaging, Hematology, and Oncology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14040-900, Brazil; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Onabajo O; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Mills GC; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Schmid V; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.
  • Brodie SA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Delattre O; INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris 75248, France.
  • Mole DR; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.
  • Purdue MP; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Yu K; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Brown KM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA. Electronic address: chanocks@mail.nih.gov.
Am J Hum Genet ; 108(9): 1590-1610, 2021 09 02.
Article en En | MEDLINE | ID: mdl-34390653
ABSTRACT
Our study investigated the underlying mechanism for the 14q24 renal cell carcinoma (RCC) susceptibility risk locus identified by a genome-wide association study (GWAS). The sentinel single-nucleotide polymorphism (SNP), rs4903064, at 14q24 confers an allele-specific effect on expression of the double PHD fingers 3 (DPF3) of the BAF SWI/SNF complex as assessed by massively parallel reporter assay, confirmatory luciferase assays, and eQTL analyses. Overexpression of DPF3 in renal cell lines increases growth rates and alters chromatin accessibility and gene expression, leading to inhibition of apoptosis and activation of oncogenic pathways. siRNA interference of multiple DPF3-deregulated genes reduces growth. Our results indicate that germline variation in DPF3, a component of the BAF complex, part of the SWI/SNF complexes, can lead to reduced apoptosis and activation of the STAT3 pathway, both critical in RCC carcinogenesis. In addition, we show that altered DPF3 expression in the 14q24 RCC locus could influence the effectiveness of immunotherapy treatment for RCC by regulating tumor cytokine secretion and immune cell activation.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromosomas Humanos Par 14 / Carcinoma de Células Renales / Proteínas de Unión al ADN / Factor de Transcripción STAT3 / Sitios Genéticos / Neoplasias Renales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Am J Hum Genet Año: 2021 Tipo del documento: Article País de afiliación: Brasil

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromosomas Humanos Par 14 / Carcinoma de Células Renales / Proteínas de Unión al ADN / Factor de Transcripción STAT3 / Sitios Genéticos / Neoplasias Renales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Am J Hum Genet Año: 2021 Tipo del documento: Article País de afiliación: Brasil