Loss of heterozygosity on chromosome 10 is more extensive in primary (de novo) than in secondary glioblastomas

Glioblastomas develop de novo (primary glioblastomas) or through progressio n from low-grade or anaplastic astrocytoma (secondary glioblastomas). There is increasing evidence that these glioblastoma subtypes develop through di fferent genetic pathways. Primary glioblastomas are characterized by EGFR a nd MDM2 amplification/overexpression, PTEN mutations, and p16 deletions, wh ereas secondary glioblastomas frequently contain p53 mutations. Loss of het erozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic al teration in glioblastomas; the involvement of tumor suppressor genes, other than PTEN, has been suggested. We carried out deletion mappings on chromos ome 10, using PCR-based microsatellite analysis. LOH#10 was detected at sim ilar frequencies in primary (8/17; 47%) and secondary glioblastomas (7/13; 54%). The majority (88%) of primary glioblastomas with LOH#10 showed LOH at all informative markers, suggesting loss of the entire chromosome 10. In c ontrast, secondary glioblastomas with LOH#10 showed partial or complete los s of chromosome 10q but no loss of 10p. These results are in accordance wit h the view that LOH on 10q is a major factor in the evolution of glioblasto ma multiform as the common phenotypic end point of both genetic pathways, w hereas LOH on 10p is largely restricted to the primary (de novo) glioblasto ma.