Tumor genomic profiling and TP53 germline mutation analysis of first-degree relative familial gliomas

About 5% of gliomas occur in a familial context, which suggests a genetic origin, but the predisposing molecular factors remain unknown in most cases. A series of nine familial gliomas were characterized with 1-megabase resolution BAC array-based comparative genomic hybridization (aCGH) together with germline sequence analysis of TP53. This series was compared with a literature series of familial gliomas and a personal series of sporadic gliomas, analyzed by chromosome CGH and aCGH, respectively. No significant difference was noted between the three populations in terms of clinical characteristics, pathologic features, and the most frequent chromosomal alterations, including loss of 1p, 10p, 10q, 13q, and 19q, and gain of 7p, 7q, 16p, 18q, 19p, 19q, 20p, and 22q. However, a genomic region located in 6q was more frequently gained in our series of familial as compared to sporadic gliomas (P=0.028). A germline TP53 mutation was observed in 1/9 cases, which suggests Li-Fraumeni syndrome. Interestingly, the Pro allele in the codon 72 of TP53 was observed in 5/9 tumors. Although familial and sporadic gliomas share very similar cytogenetic quantitative patterns, aCGH is a promising technique for the detection of small genomic differences of potential significance.