Mapping of chromosomal gains and losses in primitive neuroectodermal tumors by comparative genomic hybridization

Abstract

A series of 18 primitive neuroectodermal tumors (PNETs), the most common malignant central nervous system tumors of childhood, were analyzed with the recently developed approach of comparative genomic hybridization (CGH). In five cases, in which only small amounts of DNA were available, universal polymerase chain reaction was successfully applied to generate adequate probe material. In 15 tumors, chromosomal imbalances were elicited, most frequently involving chromosome 17 (loss of 17p and gain of 17q). Further recurrent imbalances included gains of the distal regions of 4p, 5p, 5q, 7q, 8q, and 9p. High-level amplifications were found on 2p24 (one case) and 8q24 (three cases), suggesting involvement of the protooncogenes MYCN and MYC, respectively. In one of these cases, Southern blot analysis could be performed, proving high-copy-number amplification of MYC. Interestingly, none of the three patients with high-copy-number amplifications of MYC responded to therapy.

Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system

“…We found amplification on chromosome 7 in one MB, but all the long arm of chromosome 7 was amplified. The frequency of MYCN and MYC amplification detected in our study was similar to those estimated in Schutz et al 17 They found MYCN amplification in one of 18 MB (6%), and three of 18 (17%) showed MYC amplification.…”

“…While for some authors it varies from 30% to 44%, 2,15,16 for other groups this frequency is lower. 17,18 Gilhuis et al 18 did not find gains of the entire chromosome 7, but of the 7q11 band in two of 10 MB, while Schutz et al 17 detected gains on 7q in one of 18 cases (6%). In contrast, this alteration was rarely found in sPNET: only one of the six sPNET tumours presented a gain of chromosome 7.…”

Characteristic Chromosomal Imbalances in Primary Central Nervous System Lymphomas of the Diffuse Large B‐Cell Type

“…To circumvent this problem, we employed universal DNA-amplification by DOP-PCR prior to CGH analysis. We and others had successfully used this approach for the analysis of small cell samples (3,27,47,49,54,58). In this study, application of a modified DOP-PCR protocol enabled us to perform high-quality CGH from stereotactic biopsy samples.…”

Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN , MET , WNT2 , and ERBB2

“…One of the novel amplified protooncogenes identified by this approach was MYCN (tumor 19). Amplification of this gene has been observed in tumors of neuroepithelial origin, in particular in neuroblastomas (Schwab et al, 1983;Brodeur et al, 1984;Kohl et al, 1984), but also in some astrocyto- mas (Garson et al, 1985), medulloblastomas (Fuller and Bigner, 1992;Schü tz et al, 1996), and a few cases of retinoblastoma (Lee et al, 1984). MYCN amplification was also described in nonneuronal cells derived from small-cell lung cancer (Nau et al, 1986), although these cells were shown to express neuroendocrine-specific isoenzymes (Gazdar et al, 1985).…”