Chromosome analysis of brain tumors in childhood

Abstract

We performed a chromosome analysis of 26 pediatric brain tumors, including 20 primitive neuroectodermal tumors (PNETs). 5 astrocytomas, and 1 immature teratoma. Specimens were treated with collagenase, placed in overnight or short-term cultures, and harvested for chromosome analysis. Numerical and/or structural abnormalities were noted in 14 of the 20 PNETs and 4 of the 5 astrocytomas. In 13 PNETs, so-called medulloblastoma in the cerebellum, an i(17q) was the most frequent structural abnormality, accounting for 30% (4/13). Double minute chromosomes (dmin) were observed in one tumor. Near-diploidy was demonstrated in three of these PNETs, hyperdiploidy in three, and near-tetraploidy in three. We could not find any correlation of these cytogenetic findings with the prognosis. In the remaining seven PNETs other than medulloblastoma, the karyotypes of five PNETs demonstrated a variety of numerical and structural abnormalities. As to the astrocytomas, losses of chromosomes 7 and 9 with dmin were observed in two, and structural abnormalities of chromosomes 1 and 17 were also observed in two tumors. In our limited cases, however, we could not find the same chromosome abnormalities that are well known in adult astrocytomas. A congenital immature teratoma showed hyperdiploidy with increased numbers of chromosomes 3, 6, and 12. We conclude that i(17q) is an important chromosome abnormality in medulloblastomas, and that the oncogenesis of pediatric astrocytomas might be different cytogenetically from that of adult astrocytomas.

Comparative genomic hybridization detects many recurrent imbalances in central nervous system primitive neuroectodermal tumours in children

“…Because of difficulties in generating adequate metaphases, cytogenetic data in these tumour types are still limited. The most frequent abnormality is isochromosome i(17q), found in approximately 30% of cases analysed with conventional cytogenetics (Bigner et al, 1988;Griffin et al, 1988;Biegel et al, 1989;Karnes et al, 1992;VagnerCapodano et al, 1992;Neumann et al, 1993;Fujii et al, 1994). This high incidence of i(17q) was confirmed in a molecular cytogenetic study, which also showed deletions of 17p in 44% of patients (Biegel et al, 1995).…”

“…A very recent deletion mapping study localized a common chromosomal disruption within a more centromeric region, at 17p11.2 (Scheurlen et al, 1997). Other recurrent abnormalities have been described, including structural aberrations of chromosomes 1, 3, 6, 11, 16 and X, loss of chromosome 22 and gains of chromosomes 6 and 8 (Farwell et al, 1977;Bigner et al, 1988Bigner et al, , 1990Griffin et al, 1988;Callen et al, 1989;Karnes et al, 1992;Neumann et al, 1993;Fujii et al, 1994). Few gene amplifications have been reported, involving MYC, MYCN or EGFR (Rouah et al, 1989;Wasson et al, 1990;Fuller and Bigner, 1992;Badiali et al, 1995), and more recently the 5p15 and 11q22 chromosomal regions (Reardon et al, 1997).…”

Molecular cytogenetic analysis in the study of brain tumors: findings and applications

“…Whereas ependymomas occur in both children and adults, subependymomas and myxopapillary ependymomas are more common in adults. 267 The CGAP website identifies 106 ependymoma karyotypes 1,22,50,62,64,83,92,117,161,175,207,209,225,227,257,270,278,281,293,294 (also reviewed by Mazewski,et al 161 ). The karyotypes described are predominantly normal, and when abnormal are near-diploid, and are characterized by gains and losses of entire chromosomes.…”

“…The CGAP website combines the two major subgroups, yielding 185 cases. 13,[22][23][24]28,30,50,83,92,175,225,232,278,282 More than 75% of the karyotypes are diploid or near-diploid, with the remaining 25% tetraploid and triploid. Whole chromosomal gains and losses are common and include gains of 1, 3, 4, 6, 7, 8, 17, and 18 and losses of 9, 10, 12, 13, and 19.…”

“…The CGAP website reports three ependymoblastomas, 83 with diploid karyotypes in two cases and a hypotriploid karyotype in the third. In one diploid case, the sole aberration was the gain of chromosome 22.…”