Comparative genomic hybridization indicating two distinct subgroups of pilocytic astrocytomas

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>The authors investigated the spectrum of chromosomal imbalances of pilocytic astrocytoma by using comparative genomic hybridization (CGH).</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Tumor DNA was extracted from surgically obtained samples of 18 pilocytic astrocytomas that were examined for the presence of neoplastic tissue on frozen sections. Comparative genomic hybridization was performed using standard procedures, and digital image analysis was conducted using out by custom-made software. The chromosomal alterations were determined by a statistical procedure in which Student's t-test (99% confidence interval) was used. Details on CGH analysis and individual ratio profiles are available at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://amba.charite.de/cgh/" xlink:type="simple">http://amba.charite.de/cgh/</jats:ext-link>.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The results suggests the presence of two distinct genetic subgroups of pilocytic astrocytoma, with imbalances of chromosome 19 being the major change for differentiation. In the first group (10 samples), deletions on chromosome 19 were shown as well as multiple gains mainly on chromosomes 5 and 6q but also on chromosomes 4, 7, 8, 10, and 11. The second group (eight samples) was characterized by overrepresentation on chromosomes 19p and 22q, which were associated with deletions on 4q, 5q, 6q, 9p, 13q, and 18q. To understand the diverse biological and clinical behavior exhibited by this tumor type, it is important that pilocytic astrocytomas be classified into distinct subgroups according to their genetic makeup.</jats:p></jats:sec>

Intratumoral genetic heterogeneity in pilocytic astrocytomas revealed by CGH-analysis of microdissected tumor cells and FISH on tumor tissue sections

“…Gains of 4q and 6q appeared to be more pronounced in biphasic areas, whereas gains of 6 and 8q seemed to be more common in pleomorphic areas. These genetic aberrations are confirmed by CGH studies on homogenized tumor samples in a lower frequency (12)(13)(14)(15) and are also observed in low grade astrocytomas (30). With this specific approach it was possible to show the first evidence of a correlation of different morphologic areas with specific genetic changes.…”

“…Comparative genomic hybridization analysis (CGH) showed similar results, affecting several chromosomes including aneuploidy for chromosomes 7 and 8 (12)(13)(14)(15). Fluorescence in situ hybridization (FISH) on isolated nuclei from paraffin embedded material revealed comparable results (16).…”

Genomic Analysis of Pilocytic Astrocytomas at 0.97 Mb Resolution Shows an Increasing Tendency Toward Chromosomal Copy Number Change With Age

“…Using R-banding and classic cytogenetics, Zattara-Cannoni et al reported chromosomal abnormalities in 13 of 24 cases, including gains of chromosomes 7 and 8 in 3 cases each with a further 6 cases showing random gains or losses (24). A metaphase comparative genomic hybridization (CGH) study reported a pattern of multiple small gains and losses (22).…”

The Potential Role of Environmental Exposures and Genomic Signaling in Development of Central Nervous System Tumors

“…These gains were not found in one study of low-grade astrocytomas [166], however another study identified trisomy 7 in this tumor type [167]. and 22q [188]. Cytogenetic abnormalities appear unrelated to pediatric low-grade astrocytoma prognosis [189].…”