Cytogenetic tetraclonality in a rare spindle cell variant of an anaplastic carcinoma of the thyroid.

We report a case of an unusual anaplastic carcinoma with spindle cell differentiation in an 85-year-old patient. Although the tumor showed sarcoma-like features its occurrence in the thyroid of an elderly person supported the diagnosis of an anaplastic carcinoma. This diagnosis is also supported by the results of cytogenetic studies that revealed four independent clones. Of these, three clones showed complex chromosomal rearrangements including translocations, deletions and inversions while the remaining clone only showed two balanced translocations. The patient is still alive after 13 months.

A malignant triton tumor with an unbalanced translocation (1;13)(q10;q10) and an isochromosome (8)(q10) as the sole karyotypic abnormalities.

The karyotype of a malignant nerve sheath tumor with rhabdomyosarcomatous differentiation (malignant triton tumor) of a 58-year-old woman is reported. The tumor revealed an isochromosome for the long arm of chromosome 8 and an unbalanced translocation (1;13)(q10;q10) leading to a gain of the long arm of chromosome 1 as the sole karyotypic abnormalities.

Chromosomal translocations affecting 12q14-15 but not deletions of the long arm of chromosome 7 associated with a growth advantage of uterine smooth muscle cells.

Cytogenetically, uterine leiomyomata are the best investigated human tumours. The most frequent clonal abnormalities are structural rearrangements involving 12q14-15 and deletions of part of the long arm of chromosome 7. The present study investigated a possible growth advantage conferred by these abnormalities, when compared with myomata having an apparently normal karyotype. A total of 155 myomata were included in the study. All samples were obtained after hysterectomy enabling karyotype analysis of all detectable tumours. Myomata with clonal chromosome abnormalities were significantly larger than those with a normal karyotype (6.8 +/- 5.3 versus 3.4 +/- 2.1 cm; P < 0.001). However, when differentiating between the two main aberrations, this was found to be true for the myomata with 12q14-15 changes affecting the high mobility group protein IC (HMGIC) gene (8.9 +/- 5.6 cm), but not for the group of tumours characterized by deletions of chromosome 7 (3.5 +/- 2.0 cm). The results are compatible with the hypothesis that myomata develop due to an unknown event, whereas the chromosomal abnormalities act as secondary changes, with those affecting the HMGIC gene increasing the growth potential of the corresponding tumours.

Structural abnormalities of chromosome 2 in benign thyroid tumors. Three new cases and review of the literature.

Here we report our cytogenetic findings on three cases of nodular goiter, all showing structural clonal abnormalities of chromosome 2. In the first case, we found a t(2;3)(q21;q27 or q28) in two nodules of the same patient. The second case revealed a t(2;20;3)(p21;q11.2;p25), and the third case showed a t(1;2)(p22;p13). When the data from the literature and the present cases are summarized, the results suggest the existence of at least three breakpoint clusters of chromosome 2 in benign thyroid tumors or hyperplasias.

Cytogenetic analysis of three oropharyngeal malignant melanomas in dogs.

Three cases of histologically confirmed oropharyngeal malignant melanomas in dogs are presented including clinical examinations and cytogenetic analysis. Case one showed a hyperdiploid karyotype. Case two, a recurrent tumour, had a highly hypodiploid karyotype with supernumerary meta- and submetacentric chromosomes in all metaphases analysed. In the third case, a clonal fusion of chromosome 1 and 25 was observed. Comparing these results with another case of canine cutaneous melanoma as well as with human malignant melanomas reported in the literature, these tumours obviously often show cytogenetic aberrations like aneuploidy and centric fusions.

A high frequency of tumors with rearrangements of genes of the HMGI(Y) family in a series of 191 pulmonary chondroid hamartomas.

Pulmonary chondroid hamartomas (PCHs) are benign mesenchymal tumors that often are characterized by specific chromosomal aberrations. Herein we report our cytogenetic and molecular cytogenetic (FISH) studies on 191 PCHs, including 48 previously published cases. In this series, 134/191 PCHs (70.2%) showed either abnormalities of chromosomal bands 6p21 (21 tumors), 12q14-15 (95 tumors), or had other abnormalities (18 tumors). Two tumors had a 6p21 aberration together with a 12q14-15 aberration. The most frequent translocations were t(12;14)(q15;q24) (19 cases) and t(6;14)(p21. 3;q24) (18 cases), both in either simple or complex form. By FISH with cosmids spanning the gene encoding the high-mobility-group protein HMGIC, we were able to show a rearrangement within or close to HMGIC in all tumors with 12q14-15 abnormalities tested, in 11 tumors with an apparently normal karyotype, and in 4 tumors with complex abnormalities without cytogenetically visible alterations of chromosomes 12. Rearrangements of HMGIY or its immediate surroundings were shown for 21 cases with 6p21 aberrations and three cases with other chromosomal abnormalities but without cytogenetically visible alterations of chromosomes 6. Genes Chromosomes Cancer 26:125-133, 1999.

Cytogenetic investigation of canine lipomas.

Akin to humans, lipomas are common in the dog as well; however, until now there were no reports of cytogenetic investigations on these tumors in the canine. We report our results of cytogenetic investigations on a series of ten canine lipomas. Clonal aberrations were observed in seven cases. In one case a trisomy 27 was evident; in another case a trisomy 13 was present in addition to a marker chromosome. A third lipoma showed a fusion of chromosomes 2 and 13. These cases showed one derivative chromosome each (der(X), der(7), and der(4)), and one case had two derivative chromosomes (der(X) plus der(4)). In the two cases with derivative chromosomes 4, the same region (4q31) was affected. It is tempting to speculate that this region might harbor a gene associated with tumor development. The results are compared to the cytogenetic situation in human lipomas.

Pleomorphic adenomas of the salivary glands: absence of HMGIY rearrangements.

Rearrangements of chromosome region 12q14-15 affecting the HMGIC gene are a frequent finding in benign solid tumors. Another non-random chromosomal alteration observed in subgroups of several of the tumor entities with 12q14-15 changes are rearrangements of 6p21 resulting in alterations of the HMGIY gene, which have so far not been documented in pleomorphic adenomas of the salivary glands. In our series of 335 pleomorphic adenomas, karyotypic changes affecting chromosomal region 6p21-23 were observed in five tumors all showing either a simple or complex t(6;8)(p21-p23;q12). Molecular cytogenetic studies of two of these tumors revealed that the 6p-breakpoint of this translocation maps distal to HMGIY, not affecting the gene or its closer vicinity. The results strongly suggest that pleomorphic adenomas are the only exception to the rule that entities of benign tumors with HMGIC rearrangements also have subtypes with HMGIY rearrangements. The difference from the other tumors is discussed in terms of tissue specificity of both HMG protein genes.

Working with canine chromosomes: current recommendations for karyotype description.

There is an increasing interest in genomic research on the domestic dog (Canis familiaris). However, these investigations are complicated by the canine karyotype comprising 76 acrocentric autosomes of similar size and shape and the metacentric sex chromosomes. None of the numerous published ideograms and karyotypes has yet been generally accepted. The present article gives a review of these descriptions of the canine karyotype. The two most recent nomenclatures and the current efforts toward a standardized canine karyotype made by the Committee for the Standardized Karyotype of the Dog are discussed in detail and recommendations for future use of a nomenclature for the canine karyotype are given.

Karyotype evolution in a case of uterine angioleiomyoma.

Clonal karyotypic alterations of a uterine angioleiomyoma of a 41-year-old woman are reported. Cytogenetically a stemline of the tumor and two related subclones with additional abnormalities due to karyotypic evolution were identified: 46,X,t(X;11)(p11.4;p15)/46, idem,inv(2)(p15q13)/46, idem,inv(2)(p15q13),t(5;20)(q13;q13.2). None of the aberrations observed in the present case has been reported in uterine smooth muscle tumors before.

Two cases of fibrocystic breast disease with polysomy 18 as the sole clonal cytogenetic abnormality.

In the present study, we describe the occurrence of numerical alterations of chromosome 18 in two cases of benign fibrous/fibrocystic tumors of the breast, both of which were studied by conventional cytogenetic investigations and one of which was additionally tested by fluorescence in situ hybridization with the use of an alphoid centromeric probe specific for chromosome 18. Case 1 showed a tetrasomy 18 in 2 of 33 metaphases as the only clonal chromosomal aberration. Case 2 revealed both trisomy and tetrasomy 18 as clonal alterations in metaphases and interphase nuclei.

Follicular thyroid carcinoma: chromosome analysis of 19 cases.

Short-term cultures of 19 follicular thyroid carcinomas were examined cytogenetically. Clonal chromosomal changes were detected in 12 tumors. Two follicular carcinomas had only numerical alterations: one with a hyperdiploid karyotype with trisomies/polysomies of chromosomes 7 and 12, similar to the karyotypes previously identified in a sub-group of benign thyroid lesions, and the other with monosomy 20. In the remaining ten cases several structural chromosome anomalies were found. Loss of the short arm of chromosome 3 was observed in one tumor. In two widely invasive and metastasizing follicular carcinomas there was a t(7;8)(p15;q24) as the sole abnormality in one case and a der(8)t(7;8)(p15;q24) together with other cytogenetic alterations in the other case. This finding suggests that t(7;8)(p15;q24) may be related to an aggressive behavior of follicular thyroid carcinomas.

Cloning and molecular characterization of part of a new gene fused to HMGIC in mesenchymal tumors.

Aberrations of the HMGIC gene, encoding an architectural transcription factor and located in the chromosomal region 12q15, are very frequent among benign mesenchymal tumors, such as lipomas, uterine leiomyomas, or pulmonary chondroid hamartomas. These HMGIC aberrations are caused by characteristic structural chromosomal aberrations, either visible by conventional cytogenetics or as cryptic abnormalities. Some of these aberrations of chromosome 12 are not specific for particular tumor entities but can occur in a variety of tumors with HMGIC abnormalities. One such example is the pericentric inversion inv(12)(p11.2q15). Starting from the ectopic sequence derived from an HMGIC fusion transcript of an aggressive angiomyxoma with such an inversion we established three PAC clones covering the breakpoint region 12p11 and cloned part of a yet unknown gene in 12p11.2, which is fused to the third exon of HMGIC. Using fluorescence in situ hybridization with these PACs we were able to show that the same region was involved by 12p11.2 aberrations in lipomas, aggressive angiomyxomas, and pulmonary chondroid hamartomas.

Cytogenetic investigations of 340 thyroid hyperplasias and adenomas revealing correlations between cytogenetic findings and histology.

Cytogenetic analyses were performed on 340 follicular thyroid adenomas and goiters after short-term culture. Clonal chromosomal changes were found in 67 cases. Trisomy 7 as the sole abnormality or along with other trisomies was the most frequent type of aberration (19 cases). Other recurrent numerical changes were loss of chromosome 22 (4 cases) and the second X or the Y chromosome (5 cases). Translocations involving 19q13 (12 cases) were frequent structural chromosomal changes. Dicentric chromosomes or telomeric associations were frequent in goiters (12 cases). After a histopathologic classification of all cases, we have correlated the cytogenetic findings with the histology of the tumors. Only 8.4% of the goiters showed clonal abnormalities, whereas 44.9% of the adenomas revealed clonal abnormalities. Furthermore, simple clonal changes were predominantly found in goiters and complex changes in adenomas. The most impressive correlation was found in the group of lesions with trisomy 7. Although all but one lesion with one or two additional trisomies were goiters, those having three or more additional trisomies were all adenomas or adenomatous goiters.

Trisomy 1 in a canine acute leukemia indicating the pathogenetic importance of polysomy 1 in leukemias of the dog.

We report on a canine acute myeloid leukemia showing a trisomy 1 and a t(X;8) as clonal cytogenetic abnormalities. Comparing these results with similar cases of canine leukemias reported in the literature, one realizes that trisomy 1 is a recurrent cytogenetic finding in canine acute leukemia. Trisomy 1 may be a specific anomaly associated with either etiology or progression of this disease. As with comparable human neoplasms, cytogenetic investigations could be of diagnostic and prognostic significance for canine hematopoietic diseases. Moreover, as trisomies are recurrent cytogenetic findings in human leukemias, as well, comparative gene mapping in future studies may help to focus the etiologic basis of the disease to particular chromosomal segments instead of whole chromosomes.

A third case of a low-grade endometrial stromal sarcoma with a t(7;17)(p14 approximately 21;q11.2 approximately 21).

Cytogenetic analysis of a low-grade endometrial stromal sarcoma of the uterus in a 52-year-old woman revealed the karyotype 46,XX,t(7;17)(p14 approximately 21;q11.2 approximately 21),der(7)t(7;16)(p14-15;q22)t(7;9) (q22;q22), der(9)t(7;9)(q22;q22),del(16)(q22). The t(7;17) was identical to an aberration observed in two other cases of endometrial stromal sarcomas, thus confirming the idea that it constitutes a non-random aberration for this type of tumor.

Breakpoints of 19q13 translocations of benign thyroid tumors map within a 400 kilobase region.

Structural rearrangements involving the long arm of chromosome 19 characterize a cytogenetic subgroup of benign thyroid tumors. To localize the breakpoint of the 19q13 aberrations, we have established three cell lines derived from benign thyroid tumors showing translocations in this region. We have used these cell lines and four additional primary tumors with 19q13 abnormalities for fluorescence in situ hybridization (FISH) mapping studies with ten cosmid clones located between the molecular markers POLD1 and TNNT1. The breakpoints of all chromosome 19 abnormalities mapped within a 400 kb region.