Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization

Abstract

Comparative genomic hybridization (CGH) is a technique that allows the detection of losses and gains in DNA copy number across the entire genome. We used CGH to study the genetic alterations that occur in primary astrocytomas, including 14 glioblastomas (GBM), 12 anaplastic astrocytomas (AA), and 7 low‐grade astrocytomas (LGA). The average numbers of total aberrations in GBM, AA, and LGA were 9.7, 5.4, and 4.0, respectively. The average number of DNA sequence losses in GBM was significantly higher than that in AA or LGA (P < 0.01). Frequently altered regions (> eight cases) observed in all grades of astrocytoma were 7p13‐p12 (gain), 7q31 (gain), 8q24.1‐q24.2 (gain), 9p21 (loss), 10p12‐p11 (loss), 10q22‐qter (loss), 13q21‐q22 (loss), and 20q13.1‐q13.2 (gain). Loss of 9p, 10p, or 10q, and the gain or amplification of 7p, were observed frequently in GBM (64%, 57%, 64%, and 50% of cases, respectively). Frequent alterations found in AA were losses of 9p, 10q, and 13q, and gains of 1q, chromosome 7, 11q, and Xq. Whereas 7p13‐p11 amplification occurred exclusively in cases with the loss of all or part of chromosome 10, this change never occurred in cases having an increase in copy number of 8q, which was the most frequent change observed in LGA (four of seven cases). These results may indicate that an increase in copy number of 8q is an important event in GBM, with a genetic pathway, which is distinct from that in GBM with 7p amplification. Genes Chromosomes Cancer 21:340–346, 1998. © 1998 Wiley‐Liss, Inc.

Chromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutation

“…The glioblastomas of patients D and A were near tetraploid, but still showed proportional loss of several chromosome arms. All three glioblastomas showed deletion of 9p, a change known to be common in sporadic glioblastomas Mohapatra et al, 1995;Nishizaki et al, 1998;Schlegel et al, 1996;Weber et al, 1996). This common deletion involves 9p21 where the CDKN2A gene, coding for p16, an inhibitor of cyclin dependent kinases, is situated.…”

High-resolution genome-wide allelotype analysis identifies loss of chromosome 14q as a recurrent genetic alteration in astrocytic tumours

“…Mutation of the TP53 gene, which is located on 17p, is the most common genetic alteration detected in 460% tumours (von Deimling et al, 1992a). Gains of chromosomal arms 7q and 8q are also detected in a subset of low-grade astrocytic tumours (Schrock et al, 1996;Nishizaki et al, 1998). Moreover, low-grade astrocytic tumours often recur with concomitant malignant progression to anaplastic astrocytomas or glioblastomas by acquiring additional genetic changes.…”

Interspecies Comparative Genomic Hybridization (I-CGH): A New Twist to Study Animal Tumor Models

“…CGH allows rapid screening of DNA copy number alterations across the entire genome. CGH analyses have been used to analyze a variety of solid tumors, 3 including gliomas [4][5][6][7][8][9][10][11][12] to reveal a number of common aberrations associated with neoplastic transformation and cancer. In addition, CGH permits comparisons of genetic differences between normal or pre-malignant and malignant states using only minute portions of tissue, as well as discerning differences between individual tumors.…”