title: Loss of heterozygosity on chromosome 19 in secondary glioblastomas.
abstract: Glioblastomas develop rapidly de novo (primary glioblastomas) or slowly through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). Recent studies have shown that these glioblastoma subtypes develop through different genetic pathways. Primary glioblastomas are characterized by EGFR amplification/overexpression, PTEN mutation, homozygous p16 deletion, and loss of heterozygosity (LOH) on entire chromosome 10, whereas secondary glioblastomas frequently contain p53 mutations and show LOH on chromosome 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. LOH on chromosome 19q was frequently found in secondary glioblastomas (7 of 13, 54%) but rarely detected in primary glioblastomas (1 of 17, 6%, p = 0.0094). The common deletion was 19q13.3 (between D19S219 and D19S902). These results suggest that tumor suppressor gene(s) located on chromosome 19q are frequently involved in the progression from low-grade astrocytoma to secondary 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 in 38% of secondary glioblastomas and typically included the RB locus. Except for 1 case, LOH 13q and 19q were mutually exclusive.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yonekawa
authors.forename: P
authors.initials: P
authors.lastname: Kleihues
authors.forename: H
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D001254:Astrocytoma; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D018450:Disease Progression; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity