Journal article

High Frequency of Germline TP53 Mutations in a Prospective Adult-Onset Sarcoma Cohort

G Mitchell, ML Ballinger, S Wong, C Hewitt, P James, MA Young, A Cipponi, T Pang, DL Goode, A Dobrovic, DM Thomas, S Porceddu, M Gattas, S Neuhaus, G Suthers, M Tattersall, K Tucker, C Lewis, R Carey-Smith

Plos One | PUBLIC LIBRARY SCIENCE | Published : 2013

Abstract

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 ..

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