Loss of heterozygosity on chromosome 19 in secondary glioblastomas

Glioblastomas develop rapidly de novo (primary glioblastomas) or slowly thr ough progression from low-grade or anaplastic astrocytoma (secondary gliobl astomas). Recent studies have shown that these glioblastoma subtypes develo p through different genetic pathways. Primary glioblastomas are characteriz ed by EGFR amplification/overexpression, PTEN mutation, homozygous p16 dele tion, and loss of heterozygosity (LOH) on entire chromosome 10, whereas sec ondary glioblastomas frequently contain p53 mutations and show LOH on chrom osome 10q. In this study, we analyzed LOH on chromosomes 19q, 1p, and 13q, using polymorphic microsatellite markers in 17 primary glioblastomas and in 13 secondary glioblastomas that progressed from low-grade astrocytomas. LO H on chromosome 19q was frequently found in secondary glioblastomas (7 of 1 3, 54%) but rarely detected in primary glioblastomas (1 of 17, 6%, p = 0.00 94). The common deletion was 19q13.3 (between D19S219 and D19S902). These r esults suggest that tumor suppressor gene(s) located on chromosome 19q are frequently involved in the progression from low-grade astrocytoma to second ary glioblastoma, but do not play a major role in the evolution of primary glioblastomas. LOH on chromosome 1p was detected in 12% of primary and 15% of secondary glioblastomas. LOH on 13q was detected in 12% of primary and i n 38% of secondary glioblastomas and typically included the RE locus. Excep t for 1 case, LOH 13q and 19q were mutually exclusive.