Abstract B10: Germline copy number variation in Li-Fraumeni syndrome patients with TP53 mutations

Abstract

Abstract Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited disorder characterized by a remarkably increased risk of early-onset and multiple cancers, including breast, brain tumors and other neoplasms in individuals carrying germline TP53 mutations. The specific presence of constitutional copy number variation of large DNA segments (CNV) in LFS individuals may either represent a cancer susceptibility factor or result from a genetic instability. We used a 180K oligoarray platform from Agilent to estimate the CNV frequencies in 21 unrelated Li-Fraumeni patients carrying TP53 mutations. We compared the resulting frequencies between these individuals (n=21) to a population based control group (n=100), and defined as “rare genomic alterations” those located in coding regions and covered by ≤3 individual CNVs described in DGV (Database of Genomic Variants). Similar frequencies of CNVs were found in both patients and control groups with an average of 7–8 CNVs per genome. Rare CNVs were significantly more frequent among cancer patients (average of 0.8 per individual) than among controls (average of 0.3 per individual) (p<0.0001). Some of the genes encompassed by the rare germline CNVs from Li-Fraumeni patients have been previously reported to be altered in tumors, but are here described for the first time as altered in germline. Funding by Fapesp and CNPq. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B10.