Genetic heterogeneity and progression in different areas within high-grade diffuse astrocytoma

The primary objective of this study was to determine loss of heterozygosity (LOH) in various portions of 9 high-grade diffuse astrocytomas, 8 glioblastomas 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 diverse morphological characteristics, a common feature of diffuse astrocytomas. In 2, 2, 3 and 1 cases, the allele losses were found within part of grade IV 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 on 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 not demonstrate genetic heterogeneity and the LOH was on the same allele, irrespective of grade, suggesting clonal origin. In conclusion, at the molecular level, the diverse morphological features of astrocytoma develops by a multistep mechanism of genetic alterations from one cell via low-grade and more malignant tumors towards glioblastoma.