Interphase cytogenetics on paraffin sections of paediatric extragonadal yolk sac tumours

Abstract

Germ cell tumours in children are more often extragonadal than in adults and the most frequent type is the yolk sac tumour. Limited cytogenetic data exist on extragonadal yolk sac tumours in children. We applied in situ hybridization (ISH) to interphase cell nuclei of four paediatric extragonadal pure yolk sac tumours and one yolk sac tumour component of a mixed germ cell tumour using paraffin-embedded tissue sections. The panel of chromosome-specific DNA probes was selected on the basis of their relevance in adult germ cell tumours and consisted of five DNA probes specific for the (peri)centromeric regions of chromosomes 1, 8, 12, and/or 17, X and/or one DNA probe specific for the subtelomeric region of chromosome 1 (p36.3). Only one tumour failed to show numerical and structural chromosome aberrations with the DNA probes used. The other four had an increased incidence of numerical chromosome aberrations with an over-representation of at least one chromosome. The DNA indices determined in the paraffin-embedded tumour material correlated well with the in situ hybridization findings. In only a few cases were chromosomes over-represented, when compared with the corresponding DNA indices. Recently, we have shown that the short arm of chromosome 1 is a non-random site of deletion in paediatric gonadal pure yolk sac tumours. The occurrence of similar deletions in one extragonadal pure yolk sac tumour and in one yolk sac tumour component, in conjunction with two further ISH reports, suggests that the loss of gene(s) in this region is an important event in the pathogenesis of paediatric malignant germ cell tumours of nearly all sites.

Chromosome abnormalities of eighty-one pediatric germ cell tumors: Sex-, age-, site-, and histopathology-related differences?a Children's Cancer Group study

“…The imbalance between sequences on 1p and 1q, particularly del(1) (p36), in pediatric GCT has been reported by several groups (Hecht et al, 1984;Perlman et al, 1994Perlman et al, , 1996Stock et al, 1994Stock et al, , 1996Jenderny et al, 1996). All of the tumors in our series that displayed this abnormality had a malignant germ cell component.…”

“…Three studies, using interphase fluorescence in situ hybridization (FISH) of paraffin-embedded pediatric GCTs, especially EST, with probes for the centromeric regions of chromosomes 1, 8, and 12, and the X chromosome, as well as the midi-satellite at 1p36, identified numerical abnormalities most commonly involving chromosome 12 and loss of 1p36 (Stock et al, 1994;Jenderny et al, 1995Jenderny et al, , 1996. These probes were chosen because of the involvement of these chromosomes in adult testicular GCT.…”

Imbalances of chromosome arm 1p in pediatric and adult germ cell tumors are caused by true allelic loss: A combined comparative genomic hybridization and microsatellite analysis

“…In contrast, Perlman et al detected loss at 1p in five of seven cases analyzed with conventional cytogenetic techniques, indicating significant observer-dependent differences in the assessment of 1p alterations (Perlman et al, 1994). Complementary FISH analyses using a 1p36 cosmid probe coupled with a centromeric or 1q probe reported a relative reduction in the number of 1p36 signals compared to the centromeric or 1q signals in up to 80% of childhood YSTs (Jenderny et al, 1996;Perlman et al, 1996;Stock et al, 1996;Bussey et al, 2001). However, since conventional chromosomal CGH revealed infrequent loss at distal 1p but frequent gain of 1q, including the centromeric region, there has been some debate whether the results of the FISH studies were related to gain of 1q rather than loss of 1p Schneider et al, 2001Schneider et al, (a), 2002.…”

Extragonadal Germ Cell Tumors: A Review With Emphasis on Pathologic Features, Clinical Prognostic Variables, and Differential Diagnostic Considerations

“…Although the majority of adult malignant GCTs have the isochromosome 12p abnormality, this aberration is very rare in children less than 10 years of age. 8 While some yolk sac tumors have shown aberrations of the short arm of chromosome 12 by interphase fluorescence in situ hybridization, 9,10 no cytogenetic abnormality has been found to specifically correlate with histology or primary tumor site in children. Aberrations of 1p, 1q, 6q, chromosome and the sex chromosomes are also frequently encountered.…”