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Germline mutation landscape of DNA damage repair genes in African Americans with prostate cancer highlights potentially targetable RAD genes.
Kohaar, Indu; Zhang, Xijun; Tan, Shyh-Han; Nousome, Darryl; Babcock, Kevin; Ravindranath, Lakshmi; Sukumar, Gauthaman; Mcgrath-Martinez, Elisa; Rosenberger, John; Alba, Camille; Ali, Amina; Young, Denise; Chen, Yongmei; Cullen, Jennifer; Rosner, Inger L; Sesterhenn, Isabell A; Dobi, Albert; Chesnut, Gregory; Turner, Clesson; Dalgard, Clifton; Wilkerson, Matthew D; Pollard, Harvey B; Srivastava, Shiv; Petrovics, Gyorgy.
Afiliação
  • Kohaar I; Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA. ikohaar@cpdr.org.
  • Zhang X; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA. ikohaar@cpdr.org.
  • Tan SH; The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Nousome D; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Babcock K; Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
  • Ravindranath L; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.
  • Sukumar G; Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
  • Mcgrath-Martinez E; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.
  • Rosenberger J; Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
  • Alba C; Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
  • Ali A; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.
  • Young D; The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Chen Y; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Cullen J; The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Rosner IL; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Sesterhenn IA; The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Dobi A; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Chesnut G; The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Turner C; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
  • Dalgard C; Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
  • Wilkerson MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.
  • Pollard HB; Urology Service, Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
  • Srivastava S; Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
  • Petrovics G; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.
Nat Commun ; 13(1): 1361, 2022 03 15.
Article em En | MEDLINE | ID: mdl-35292633
ABSTRACT
In prostate cancer, emerging data highlight the role of DNA damage repair genes (DDRGs) in aggressive forms of the disease. However, DDRG mutations in African American men are not yet fully defined. Here, we profile germline mutations in all known DDRGs (N = 276) using whole genome sequences from blood DNA of a matched cohort of patients with primary prostate cancer comprising of 300 African American and 300 European Ancestry prostate cancer patients, to determine whether the mutation status can enhance patient stratification for specific targeted therapies. Here, we show that only 13 of the 46 DDRGs identified with pathogenic/likely pathogenic mutations are present in both African American and European ancestry patients. Importantly, RAD family genes (RAD51, RAD54L, RAD54B), which are potentially targetable, as well as PMS2 and BRCA1, are among the most frequently mutated DDRGs in African American, but not in European Ancestry patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Negro ou Afro-Americano Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Negro ou Afro-Americano Limite: Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos