engleski

Glioblastomas exhibit loss of heterozygosity of the tumor suppressor gene APC

This study analyses tumor suppressor gene— adenomatous polyposis coli (APC) in 28 patients with glioblastoma, the most aggressive astrocytic form. APC protein has structural role in adherens junctions, but also plays a signaling role as a negative regulator of the wnt pathway. The etiology and pathogenesis of tumors of the central nervous system are still inadequately explained. Our interest in APC gene stemmed principally from the findings that wild-type APC protein is highly expressed in the central nervous system, and upon the finding that it is critically involved in particular syndromes, among which the brain tumors play a significant role. Glioblastoma samples were tested for gene instability by PCR/loss of heterozygosity using RFLP method. Two polymorphic markers were used: an Rsa I polymorphic site in exon 11, and an Msp I polymorphic site in exon 15. The results of our analysis for both markers showed allelic loss of the APC gene in 33.3% of our sample out of 21 heterozygous patients (heterozygosity 75%). Another 23.8% of samples demonstrated allelic imbalance of the APC allele in tumor tissue. Altogether, there were 12 samples (57%) demonstrating instability of this tumor suppressor gene. Despite increasing knowledge on glioma biology and genetics, the prognostic tools for glioblastoma still need improvement. Our findings on genomic instability of APC gene may contribute to better understanding of glioblastoma genetic profile and could be used as prognostic marker of disease evolution and progression.

glioblastoma; LOH; APC gene

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