Genome-Wide DNA Methylation Analysis Reveals Epigenetic Dysregulation of MicroRNA-34A in TP53-Associated Cancer Susceptibility
Nardin Samuel, Gavin Wilson, Mathieu Lemire, Badr Id Said, Youliang Lou, Weili Li, Diana Merino, Ana Novokmet, James Tran, Kim E Nichols, Jonathan L Finlay, Sanaa Choufani, Marc Remke, Vijay Ramaswamy, Florence MG Cavalli, Christine Elser, Lynn Meister, Michael D Taylor, Uri Tabori, Meredith Irwin Show all
Journal of Clinical Oncology | AMER SOC CLINICAL ONCOLOGY | Published : 2016
PURPOSE: Although the link between mutant TP53 and human cancer is unequivocal, a significant knowledge gap exists in clinically actionable molecular targets in Li-Fraumeni syndrome (LFS), a highly penetrant cancer predisposition syndrome associated with germline mutations in TP53. This study surveyed the epigenome to identify functionally and clinically relevant novel genes implicated in LFS. PATIENTS AND METHODS: We performed genome-wide methylation analyses of peripheral blood leukocyte DNA in germline TP53 mutation carriers (n = 72) and individuals with TP53 wild type in whom histologically comparable malignancies developed (n = 111). Targeted bisulfite pyrosequencing was performed on a ..View full abstract
Supported in part through grants from the Canadian Institutes for Health Research, Terry Fox Research Institute, and SickKids Foundation. T.J.H. is supported by a Senior Investigator Award of the Ontario Institute for Cancer Research, with funds provided by the Ontario Ministry of Research and Innovation. Establishment and running of the Children's Cancer Centre Tissue Bank at the Royal Children's Hospital Melbourne is made possible through generous support by Cancer in Kids, Leukaemia Auxiliary, the Murdoch Childrens Research Institute, and the Royal Children's Hospital Foundation.