Jannie van Echten

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

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.

Chromosomal constitution and developmental potential of human germ cell tumors and teratomas

Systematic histologic examination and adoption of a fairly standardized nomenclature for the description of the human germ cell tumors and teratomas (GCT&T) of all anatomical localizations [1-3] has led to the recognition that they contain a limited number of basic histologic components: seminoma (SE), termed dysgerminoma in the ovary, and germinoma in extragonadal localizations, and the nonseminomatous elements (NS): embryonal carcinoma (EC), yolk sac tumor (YST), choriocarcinoma, polyembryoma, immature teratoma, mature teratoma (of which the dermold cyst is a distinct, cystic variant), and spermatocytic seminoma. The GCT&T have different histologic patterns depending on their anatomical localization and the sex and the age of the patient. We propose that they can be clustered into four developmental groups on the basis of their clinical presentation and gross and microscopic morphology (Table 1):

Cytogenetic evidence that carcinoma in situ is the precursor lesion for invasive testicular germ cell tumors

A cytogenetic study of two cases of carcinoma in situ of the testis (CIS) and their adjacent invasive tumors, one a nonseminomatous germ cell tumor (NS) and one a seminoma (SE), revealed similarities in chromosomal pattern between the CIS and the invasive lesion in the same patient. These findings present for the first time cytogenetic evidence that CIS of the testis and its adjacent germ cell tumor are clonally related, which suggests that the CIS is indeed the precursor lesion of the invasive tumor.

Infantile and adult testicular germ cell tumors: a different pathogenesis?

Most adult testicular germ cell tumors have a characteristic chromosomal abnormality that is an isochromosome 12p [i(12p)]. Furthermore, these tumors are characterized by a chromosome number in the triploid range and gains and losses of (parts of) specific chromosomes. Cytogenetic investigation of three cases of infantile testicular germ cell tumors, all diagnosed as yolk sac tumors, revealed highly abnormal karyotypes. We found one case to be diploid; the other two cases were in the hypertriploid/hypotetraploid range. Structural abnormalities of chromosomes 1, 3, and 6 were recurrent and no i(12p) was found. Our results, together with data from the literature, suggest that infantile and adult testicular germ cell tumors have a different origin and pathogenetic pathway. Aberrations of chromosomes 1, 3, and 6 may play an important role in the pathogenesis of infantile testicular yolk sac tumors.

An important role for chromosome 17, band q25, in the histogenesis of alveolar soft part sarcoma

A cytogenetic study of two cases of alveolar soft part sarcoma showed near-diploid karyotypes with multiple chromosomal rearrangements. An abnormality of the long arm of chromosome 17, involving band q25, is present in both cases and in 2 of 4 cases in the literature. This recurrent structural abnormality probably plays an important role in the histogenesis of this unusual neoplasm and therefore is important for further molecular investigation.

Cytogenetics of primary testicular nonseminoma, residual mature teratoma, and growing teratoma lesion in individual patients

Residual mature teratoma (RMT) is often left behind when metastases of primary nonseminomatous germ cell tumors (NSs) are treated with chemotherapy. RMT is composed of fully differentiated somatic tissue. A growing teratoma (GTE) lesion may occur after (incomplete) resection of RMT. To shed light on tumor progression or the mechanism(s) of therapy related differentiation we investigated the chromosomal pattern of the primary NSs and RMTs in twelve patients, of the primary NS, RMT, and GTE lesion in one patient, and of the RMT and GTE lesion in two patients. Although several chromosomal differences are observed between the RMT and NSs and between the GTE and RMTs in the same patient, we obtained no evidence that specific chromosomal alteration(s) play a role in metastasis or differentiation.

Cytogenetics of a malignant ovarian germ-cell tumor

Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ‐cell tumor, composed of extensive choriocarcinoma and foci of yolk‐sac tumor, revealed a highly abnormal chromosomal pattern. We found a chromosome number in the hypertriploid/hypotetraploid range, and several clonal structural abnormalities, including 2 copies of an isochromosome 12p. We showed that the chromosomal pattern of this ovarian tumor is very similar to that of testicular germ‐cell tumors. This finding, together with reported cytogenetic data of malignant ovarian germ‐cell tumors, supports the hypothesis that ovarian and testicular germ‐cell tumors are strongly related entities that may have a similar origin and pathogenetic pathway. Int. J. Cancer 77:217–218, 1998.© 1998 Wiley‐Liss, Inc.

Cytogenetics of the progression of adult testicular germ cell tumors

This article, written on the occasion of Dr. Avery Sandbergs 75th birthday, is intended to give a general and short overview of the cytogenetic data about testicular germ cell tumors of adolescents and adults we obtained from 1983 till now. The first and last author of this manuscript visited Dr. Sandbergs lab in 1984 to improve their skills in culturing and karyotyping solid tumor cells. Knowing that cancer and progression of cancer is caused by genetic changes (i.e. changes at the chromosomal or gene level), we investigated the karyotypes of about 140 testicular germ cell tumors of the adult and adolescent male (TGCTs). The chromosomal analyses of these tumors may shed light on oncogenesis, tumor progression, pathogenetic relationship, and therapy-related differentiation. We will focus on what we think our cytogenetic data have taught us about the progression of TGCTs. Of course, a way of thinking is always influenced or even determined by the results of others. This article is not intended as a review of the literature. For this the reader should consult a recent and excellent review by Sandberg et al. [1], the manuscripts of others, and our previous publications about germ cell tumors.

Cytogenetic support for early malignant change in a diffuse neurofibroma not associated with neurofibromatosis

A 62-year-old woman presented with a solitary diffuse neurofibroma; a second recurrence showed features indicative of malignancy, but insufficient for a certain histologic diagnosis. Cytogenetic analysis revealed abnormalities previously described in malignant peripheral nerve sheath tumors and not in their benign counterparts, thus supporting the histologic suspicion of emerging malignancy.

Loss of the Y-Chromosome in the Primary Metastasis of a Male Sex Cord Stromal Tumor: Pathogenetic Implications

The first published chromosomal pattern of the retroperitoneal lymph node metastasis of a malignant gonadal stroma cell tumor of the adult testis is presented. Karyotyping showed structural chromosomal abnormalities and loss of the Y-chromosome. This loss was confirmed in primary tumor and metastasis using fluorescence in situ hybridization (FISH). The characteristic chromosomal abnormality of adult testicular germ cell tumors, an i(12p), was not present. The results are compared with other data of testicular and ovarian sex cord stromal tumors. From the comparison of the male tumors, it is concluded that loss of the Y-chromosome might have a pathogenetic significance.