2. Giant cell glioblastoma with massive loss of heterozygosity: A new molecularly defined subtype

      Giant cell glioblastoma (GCG) is a rare histologic variant of glioblastoma that is characterized by numerous bizarre, multinucleate giant cells and abundant reticulin deposition. GCG occurs in younger patients (mean age, 44 years) and generally has a better prognosis than other variants of IDH-wildtype glioblastoma. Although prior studies have identified frequent TP53 alterations in these tumors, the genomics of GCG remain poorly characterized. Herein, we describe an inter-institutional analysis of seven patients ranging from age 9 to 68 of variable race and gender diagnosed with GCG. Across 100% (7/7) of specimens in our cohort, chromosomal microarray analysis and targeted next generation sequencing consistently identified near haploidization / massive loss of heterozygosity (LOH). Remarkably, the genomic profile of these tumors showed LOH of chromosomes 3, 4, 6, 8, 13, 14, 15, 17, 22 in all cases (7/7), and LOH of chromosomes 1, 2, 5, 9, 10, 11, 18, 19 in 6/7 cases. Notably, chromosome 7 always retained heterozygosity. We propose that this genomic profile represents a distinct subtype of GCG. These findings provide evidence of an unusual mechanism of tumorigenesis and could have the potential to reveal new tumor vulnerability.
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