Fersiynau electronig

Dangosydd eitem ddigidol (DOI)

  • Stefan Meyer
  • Adam Stevens
  • Roberto Paredes
  • Marion Schneider
  • Michael J Walker
  • Andrew J K Williamson
  • Maria-Belen Gonzalez-Sanchez
  • Stephanie Smetsers
  • Vineet Dalal
  • Hsiang Ying Teng
  • Daniel J White
  • Sam Taylor
  • Joanne Muter
  • Andrew Pierce
    University of Manchester
  • Chiara de Leonibus
  • Davy A P Rockx
  • Martin A Rooimans
  • Elaine Spooncer
  • Stacey Stauffer
  • Kajal Biswas
  • Barbara Godthelp
  • Josephine Dorsman
  • Peter E Clayton
  • Shyam K Sharan
  • Anthony D Whetton
BRCA2 encodes a protein with a fundamental role in homologous recombination that is essential for normal development. Carrier status of mutations in BRCA2 is associated with familial breast and ovarian cancer, while bi-allelic BRCA2 mutations can cause Fanconi anemia (FA), a cancer predisposition syndrome with cellular cross-linker hypersensitivity. Cancers associated with BRCA2 mutations can acquire chemo-resistance on relapse. We modeled acquired cross-linker resistance with an FA-derived BRCA2-mutated acute myeloid leukemia (AML) platform. Associated with acquired cross-linker resistance was the expression of a functional BRCA2 protein variant lacking exon 5 and exon 7 (BRCA2ΔE5+7), implying a role for BRCA2 splicing for acquired chemo-resistance. Integrated network analysis of transcriptomic and proteomic differences for phenotyping of BRCA2 disruption infers impact on transcription and chromatin remodeling in addition to the DNA damage response. The striking overlap with transcriptional profiles of FA patient hematopoiesis and BRCA mutation associated ovarian cancer helps define and explicate the ‘BRCAness’ profile.
Iaith wreiddiolSaesneg
Tudalennau (o-i)e2875-e2875
CyfnodolynCell Death and Disease
Cyfrol8
Rhif y cyfnodolyn6
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 2017
Cyhoeddwyd yn allanolIe
Gweld graff cysylltiadau