Chromosomal constitution of human spermatocytic seminomas: Comparative genomic hybridization supported by conventional and interphase cytogenetics

Abstract

No data on the chromosomal constitution of spermatocytic seminomas are available thus far because of their rarity. Ploidy analysis performed on paraffin‐embedded cases showed varying results from (near‐) diploid to aneuploid. We applied comparative genomic hybridization on four snap‐frozen primary spermatocytic seminomas of three different patients. Conventional cytogenetic analysis was successful in one, and “interphase cytogenetics” with centromeric region‐specific probes was applied to another. The results from comparative genomic hybridization showed almost exclusively numerical chromosomal aberrations, in agreement with the data from karyotyping. Despite the limited number of cases studied, a nonrandom pattern of chromosome imbalances was detected: chromosome 9 was gained in all spermatocytic seminomas. This suggests that that this aberration plays a role in the development of this cancer. Interphase cytogenetics shows that the copy number of most chromosomes ranges from two to four, with an average of near trisomic. This constitutes the first report on the chromosomal constitution of spermatocytic seminomas. Genes Chromosomes Cancer 23:286–291, 1998. © 1998 Wiley‐Liss, Inc.

Whole-genome sequencing of spermatocytic tumors provides insights into the mutational processes operating in the male germline

“…The contamination of tumor DNA by normal diploid cells was shown to be minimal for most tumors, except for SpT8 that exhibited an estimated 15–20% wild-type contamination. The median autosome number was 72 (range: 50–99), confirming the extensive aneuploidy previously described for these tumors [15,26,27] (Table 1). One tumor was near-tetraploid [SpT3 (99 autosomes and 2 copies each of X and Y)], three tumors were near-triploid [SpT1 (76 autosomes and 2 copies each of X and Y), SpT6 (64 autosomes, 2 copies of X and 1 copy of Y), SpT8 (72 autosomes and 2 copies each of X and Y)], and one tumor was near-diploid [SpT4 (50 autosomes and 1 copy of X and Y)].…”

“…One tumor was near-tetraploid [SpT3 (99 autosomes and 2 copies each of X and Y)], three tumors were near-triploid [SpT1 (76 autosomes and 2 copies each of X and Y), SpT6 (64 autosomes, 2 copies of X and 1 copy of Y), SpT8 (72 autosomes and 2 copies each of X and Y)], and one tumor was near-diploid [SpT4 (50 autosomes and 1 copy of X and Y)]. For tumor SpT1, previous analyses of single cell karyotypes (performed by fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY)) are in agreement with the chromosome number obtained from relative coverage depth of the WGS data [15,27]. Hence, sequence data generated by bulk tumor DNA analysis reflect the integral chromosomal composition of the tumor.…”

“…Consistent with the characteristic presence of three different cell types observed in SpTs and cytometric analyses of DNA content [14,15], this process is likely to be relatively ‘leaky’, occasionally allowing cells to enter the differentiation pathway and initiate meiosis. Of note, SpTs are associated with a high apoptotic index that may be indicative of the failure to complete the mitosis-meiosis transition [61].…”

“…For example, cytofluorimetric analyses of DNA content have failed to show the presence of a haploid component, and mitotic figures are frequently seen in all three cell populations [14,15]. These observations suggest that SpTs occur through neoplastic transformation of pre-meiotic germ cells, probably at a transition stage between spermatogonia and spermatocytes [16].…”

On the histogenesis of mixed germ cell-sex cord stromal tumour of the gonads

“…Spermatocytic tumour shows a consistent gain in chromosome 9, a completely different chromosomal composition than that of seminoma and other malignant germ cell neoplasms;23 DMRT1 (double sex and mab-related transcription factor 1) is a candidate gene 22. Future molecular genetic studies of testicular MGC-SCST likely will be required to resolve the question of the possible relationship of the germ cells in MGC-SCST to those of spermatocytic tumour.…”