High Frequency of Germline TP53 Mutations in a Prospective Adult-Onset Sarcoma Cohort
Gillian Mitchell, Mandy L Ballinger, Stephen Wong, Chelsee Hewitt, Paul James, Mary-Anne Young, Arcadi Cipponi, Tiffany Pang, David L Goode, Alex Dobrovic, David M Thomas
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2013
Sarcomas are a key feature of Li-Fraumeni and related syndromes (LFS/LFL), associated with germline TP53 mutations. Current penetrance estimates for TP53 mutations are subject to significant ascertainment bias. The International Sarcoma Kindred Study is a clinic-based, prospective cohort of adult-onset sarcoma cases, without regard to family history. The entire cohort was screened for mutations in TP53 using high-resolution melting analysis and Sanger sequencing, and multiplex-ligation-dependent probe amplification and targeted massively parallel sequencing for copy number changes. Pathogenic TP53 mutations were detected in blood DNA of 20/559 sarcoma probands (3.6%); 17 were germline and 3 ..View full abstract
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Awarded by National Health and Medical Research Council
This work was supported by a Johanna Sewell Research Grant, the Rainbows for Kate Foundation, the Victorian Cancer Agency, and the National Health and Medical Research Council (Project Grant 1004017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.