Glioblastoma multiforme in two non-nuclear family members

In spite of traditional and current epidemiological research, there have been few environmental risk factors identified for malignant brain tumors. It has been an equally difficult challenge to identify genetic causes for brain tumors because of the rarity of families with multiple affected individuals, which prevents the use of traditional methods of genetic analysis such as genetic linkage, sib-pair, or even population-based association studies. Thus, it is important to take advantage of rare occasions of familial brain tumors.

Identification and careful study of such families may provide important clues about the etiology of brain malignancies. We studied one family of which two nonnuclear family members were affected with pathologically diagnosed glioblastoma multiforme. Fluorescence in situ hybridization (FISH) assays were used on archival sections from each patient's tumor to investigate the loss and/or gain of important allelic endpoints. Tissue sections were prepared and processed for FISH. DNA probes for targeted gene loci were used to assess allelic gain/loss. FISH probes targeted regions including 19q13, 1p36, 10q/phosphate and tensin homolog (PTEN), chromosome 3, chromosome 7, chromosome 17/17q and p53/17p.

FISH analyses identified distinct abnormalities in the two patients, suggesting that despite the familial connections and histologically similar tumors, genetic abnormalities are abundant and heterogeneous among these malignancies.

These abnormalities, however, serve to contribute to valuable information regarding patient outcomes, albeit their precise roles in the etiology of this malignancy are yet to be determined.