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Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair.
Haradhvala, Nicholas J; Polak, Paz; Stojanov, Petar; Covington, Kyle R; Shinbrot, Eve; Hess, Julian M; Rheinbay, Esther; Kim, Jaegil; Maruvka, Yosef E; Braunstein, Lior Z; Kamburov, Atanas; Hanawalt, Philip C; Wheeler, David A; Koren, Amnon; Lawrence, Michael S; Getz, Gad.
Afiliação
  • Haradhvala NJ; Massachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
  • Polak P; Massachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
  • Stojanov P; Carnegie Mellon University School of Computer Science, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA.
  • Covington KR; Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
  • Shinbrot E; Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
  • Hess JM; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
  • Rheinbay E; Massachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
  • Kim J; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
  • Maruvka YE; Massachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
  • Braunstein LZ; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
  • Kamburov A; Massachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
  • Hanawalt PC; Stanford University Department of Biology, 450 Serra Mall, Stanford, CA 94305, USA.
  • Wheeler DA; Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
  • Koren A; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Cornell University Department of Molecular Biology and Genetics, 526 Campus Road, Ithaca, NY 14853, USA.
  • Lawrence MS; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA. Electronic address: lawrence@broadinstitute.org.
  • Getz G; Massachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: gadgetz@broadinstitu
Cell ; 164(3): 538-49, 2016 Jan 28.
Article em En | MEDLINE | ID: mdl-26806129
ABSTRACT
Mutational processes constantly shape the somatic genome, leading to immunity, aging, cancer, and other diseases. When cancer is the outcome, we are afforded a glimpse into these processes by the clonal expansion of the malignant cell. Here, we characterize a less explored layer of the mutational landscape of cancer mutational asymmetries between the two DNA strands. Analyzing whole-genome sequences of 590 tumors from 14 different cancer types, we reveal widespread asymmetries across mutagenic processes, with transcriptional ("T-class") asymmetry dominating UV-, smoking-, and liver-cancer-associated mutations and replicative ("R-class") asymmetry dominating POLE-, APOBEC-, and MSI-associated mutations. We report a striking phenomenon of transcription-coupled damage (TCD) on the non-transcribed DNA strand and provide evidence that APOBEC mutagenesis occurs on the lagging-strand template during DNA replication. As more genomes are sequenced, studying and classifying their asymmetries will illuminate the underlying biological mechanisms of DNA damage and repair.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Análise Mutacional de DNA / Reparo do DNA / Neoplasias Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2016 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: Dano ao DNA / Análise Mutacional de DNA / Reparo do DNA / Neoplasias Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos