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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal


      Subscribe to Cancer Genetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect