Genetic heterogeneity and progression in different areas within high-gradediffuse astrocytoma

The primary objective of this study was to determine loss of heterozygosity (LOH) in various portions of 9 high-grade diffuse astrocytomas, 8 glioblas tomas and 1 anaplastic astrocytoma. LOH was observed on chromosomes 9, 10, 17 and 19 in 8, 3, 4 and 2 cases, respectively. Genetic heterogeneity and a multistep process were identified in 4 glioblastomas explaining the divers e morphological characteristics, a common feature of diffuse astrocytomas. In 2, 2, 3 and 1 cases, the allele losses were found within part of grade I V astrocytomas but not grades II or II/III, on chromosomes 9, 10, 17 and 19 , respectively. In one of these, while genetic heterogeneity was observed o n chromosome 17 between the area of grade II and grade IV, 9pLOH was found within both areas and occurred on the same allele. The other 5 cases did no t demonstrate genetic heterogeneity and the LOH was on the same allele irre spective nf grade, suggesting clonal origin. In conclusion, at the molecula r level, the diverse morphological features of astrocytoma develops by a mu ltistep mechanism of genetic alterations from one cell via low-grade and mo re malignant tumors towards glioblastoma.