P04.02GERMLINE REARRANGEMENTS IN FAMILIES WITH STRONG FAMILY HISTORY OF GLIOMA AND MALIGNANT MELANOMA COLON AND BREAST CANCER

摘要

BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees that include glioma as one of several cancer phenotypes to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. METHODS: Germline rearrangements in 146 glioma families from the Gliogene Consortium () with at least two glioma cases verified and a third reported or verified in the same family or two glioma cases in the family with at least one family member affected with melanoma, colon or breast cancer were examined using Multiplex Ligation dependent Probe Amplification (MLPA). The genomic areas covering TP53, CDKN2A, MLH1 and MSH2 were selected as these genes have previously been reported to be associated with cancer pedigrees known to include glioma. RESULTS: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and 1 relative with colon cancer. CONCLUSIONS: Large deletions and duplications are rare events in familial glioma cases even in families with a strong family history with cancers that may be involved in known cancer syndromes.