Detection of numerical and structural chromosome abnormalities in pediatric germ cell tumors by means of interphase cytogenetics

Abstract

In contrast to the cytogenetically well characterized testicular germ cell tumors (GCT) in adults, reports on cytogenetic studies in pediatric GCT are scarce. The presence of an i(12p) and numerical abnormalities involving chromosome 12 are the most frequent cytogenetic changes in GCT of adults. We have performed in situ hybridization (ISH) studies on paraffin sections and on isolated nuclei of 13 pediatric GCT with particular emphasis on those chromosome abnormalities that are common in adult GCT. These include numerical and structural abnormalities of chromosomes 1 and 12 as well as numerical deviations of chromosomes 8, 10, X, and Y. The histological subsets of the tumors investigated included two dysgerminomas (DGE), one seminoma (SE), two embryonal carcinomas (EC), four mixed and two pure yolk sac tumors (YST), and one undifferentiated (IT) and one differentiated teratoma (TD). Similar to the GCT in adults, additional copies of chromosome 12 were the most frequently observed numerical abnormalities. In contrast to the findings in adult GCT, changes in the size of the pericentromeric hybridization signals of chromosome 12, suggesting the presence of i(12p) chromosomes, were found in only two cases. No chromosome abnormalities were found in the pure TD or in the TD cells of mixed tumors containing a YST component. In the YST portion, however, Ip deletions and/or numerical chromosome changes were present. Surprisingly, deletions of the short arm of chromosome I, del(I)(p36.3), were frequent in pediatric GCT and were the sole abnormality detected in two cases. The Ip36 deletions were present in all stage-IV EC and YST investigated and were absent in the relatively benign TD and in one YST stage-I. Therefore, Ip36 deletions may have value as a prognostic marker in pediatric GCT.

Molecular cytogenetic analysis of adult testicular germ cell tumours and identification of regions of consensus copy number change

“…Interphase analysis using the marker for the PITSLRE locus at lp36, a candidate tumour-suppressor gene for involvement in neuroblastoma, demonstrated loss of this locus in eight out of ten paediatric cases. Similarly, Stock et al (1994) demonstrated loss of the DIZ2 locus in four GCTs of children (two testicular embryonal carcinomas and two sacral yolk sac tumours). The present study shows that the D1Z2 locus is not commonly lost in the adult TGCT and larger regions of lp are lost than in the paediatric cases.…”

Analysis of ovarian teratomas for isochromosome 12p: evidence supporting a dual histogenetic pathway for teratomatous elements

“…Evidence supporting the origin of postpubertal testicular teratomas and the teratomatous components of mixed GCTs of the testis from malignant germ cells includes their association with intratubular germ cell neoplasia, unclassified (IGCNU), 18 the presence of i(12p) and of chromosome 12p amplification in both teratomatous and nonteratomatous components of postpubertal GCTs, [19][20][21][22][23] the presence of aneuploidy in postpubertal teratomas, 22,24 the similarities in allelic losses between mature teratoma and other components of malignant mixed GCTs of the testis, 25 the malignant behavior of postpubertal testicular teratomas, [26][27][28] and the atypical cytologic appearance of some postpubertal testicular teratomas. 2,17 Conversely, evidence supporting the origin of prepubertal testicular teratomas from benign germ cells includes a lack of chromosome 12p amplification, 29 a generally diploid, 46 XY karyotype, 30 normal findings on comparative genomic hybridization studies, 31 and lack of IGCNU. 18 It is also well established that most ovarian teratomas derive from i(12p) in ovarian teratomas C Poulos et al i(12p) in ovarian teratomas C Poulos et al benign germ cells in a parthenogenetic-like fashion based on their cytogenetics, 11,12 ploidy, 32 and molecular biologic findings.…”

Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

“…The MYCN and/or 1p status of the cell lines STA-NB-3, -7, -8, -9, -10, -11, -12, -13, -15, and Vi-856 had been described previously. 37 42 Moreover, we performed FISH with the indicated probes on normal metaphase spreads to designate their chromosomal loci on chromosomes with 400 to 500 banding resolutions. …”