Trisomy 18 in a canine thyroid adenoma.

A canine thyroid adenoma showing trisomy 18 as the sole clonal cytogenetic abnormality (9 of 30 analyzed metaphases) is reported. Because trisomies are a recurrent cytogenetic finding in human benign thyroid tumors as well, it is suggested that the molecular relationship between these trisomies and the development of thyroid tumors can be determined by comparative gene mapping.

HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors.

Cytogenetically visible aberrations of chromosomal region 12q14-15 in a variety of frequent benign human tumors reflect rearrangements of the HMGI-C gene. The mechanisms by which the HMGI-C gene contributes to tumorigenesis are mostly unknown, although frequently aberrant transcripts containing exons 1 to 3 of HMGI-C and ectopic sequences from other genes due to breaks within the third intron of HMGI-C are detectable. This is the first report analyzing human tissue samples mainly of mesenchymal origin by a highly sensitive polymerase-chain-reaction-based approach detecting HMGI-C expression.

An endometrial polyp with a rearrangement of HMGI-C underlying a complex cytogenetic rearrangement involving chromosomes 2 and 12.

Cytogenetic studies of an endometrial polyp of an 82-year-old patient revealed a karyotype 46,XX,der(2)inv(2)(p25q21)ins(2;12)(p25;q13q14)t(2;12)(q21; q15),der(12)del(12)(q13q14)del(12)(q15). By fluorescence in situ hybridization (FISH) we found the chromosome 12 translocation breakpoint to be mapping within the third intron of the HMGI-C gene also harboring the breakpoints of translocations involving 12q15 seen in uterine leiomyomas, lipomas, pleomorphic adenomas, and pulmonary chondroid hamartomas.

Deletions of the short arm of chromosome 2 characterize a new cytogenetic subgroup of benign thyroid tumors.

Cytogenetic studies of thyroid hyperplasias and adenomas have shown that besides cases with an apparently normal karyotype different groups of cytogenetic abnormalities exist. Herein we describe the cytogenetic analyses of two benign thyroid tumors with deletions of the short arm of chromosome 2. A similar case has been described previously.

Transcriptional activation of HMGI-C in three pulmonary hamartomas each with a der(14)t(12;14) as the sole cytogenetic abnormality.

Aberrations involving the chromosomal region 12q14-15 are non-random cytogenetic abnormalities in many benign tumors, e.g. pulmonary chondroid hamartomas (PCH).

Rearrangements of the high mobility group protein family genes and the molecular genetic origin of uterine leiomyomas and endometrial polyps.

The results of cytogenetic studies of uterine leiomyomas have revealed that approximately 50% of these tumours are characterized by clonal chromosomal alterations. These karyotypic deviations are dominated by rearrangements involving a particular part of chromosome 12, i.e.

Significance of clonal chromosome aberrations in breast fibroadenomas.

Despite the high frequency of fibroadenomas of the breast, cytogenetic results are relatively limited. We describe our cytogenetic findings in 30 fibroadenomas. Of these, three showed clonal chromosome abnormalities, i.

Structural aberrations of chromosome 6 in three uterine smooth muscle tumors.

Clonal karyotypic alterations of chromosome 6 in three uterine smooth muscle tumors are reported. In all cases an apparently identical breakpoint on the short arm of chromosome 6 was found. Two cases displayed the histologic features of cell-rich myomas with severe nuclear atypia but no clear evidence for malignancy.

Fluorescence in situ hybridization studies on breast tumor samples for distinguishing between different subsets of breast cancer.

Objectives: To evaluate fluorescence in situ hybridization for distinguishing between malignant and benign breast tumors and determining genetic subgroups of breast cancers.

Study Design: Touch preparations from 94 surgically removed breast tumors (17 benign and 77 malignant) were hybridized with a DNA probe specific for centromeric DNA sequences of chromosome 1. Twenty samples were additionally hybridized with a chromosome 9-specific probe.

HMGI-C rearrangements as the molecular basis for the majority of pulmonary chondroid hamartomas: a survey of 30 tumors.

Pulmonary chondroid hamartomas (PCH) are benign tumors of the lung characterized by a more or less high degree of mesenchymal metaplasia. In our series we investigated 30 PCH by a combination of cytogenetic and molecular methods. 18 tumors (60%) had cytogenetically detectable aberrations involving either 12q14-15 or 6p21 with a clear predominance of chromosomal abnormalities involving 12q14-15 (15 tumors).

A fibroadenoma with a t(4;12) (q27;q15) affecting the HMGI-C gene, a member of the high mobility group protein gene family.

An intracanalicular fibroadenoma of the breast showing a clonal chromosomal aberration t(4;12) (q27;q15) as the sole cytogenetic abnormality is described. In order to narrow down the breakpoint region on chromosome 12 on the molecular level we performed fluorescence in situ hybridization (FISH) analysis with a cosmid pool originating from a YAC-contig overspanning part of the region 12q14-15. We were able to narrow down the breakpoint to an approximately 230kb fragment belonging to the HMGI-C gene which maps within an area recently designated as MAR (Multiple Aberration Region).

An extended nomenclature of the canine karyotype.

In contrast to many other animals, knowledge about the canine karyotype is quite sparse. This is due in part to the rather difficult canine karyotypic pattern. Except for the X and the Y chromosome, there are only acrocentric chromosomes, which appear to be quite small and difficult to identify unambiguously.

Mapping of the translocation breakpoints of primary pleomorphic adenomas and lipomas within a common region of chromosome 12.

Recent molecular cytogenetic analysis of uterine leiomyoma cell lines with chromosomal aberrations of 12q14-q15 have indicated that the chromosome 12 breakpoints cluster in a 445-kb region designated ULCR12 (uterine leiomyoma cluster region of the chromosome 12 breakpoints). Here we report the results of FISH studies of five primary pleomorphic adenomas and six primary lipomas and established cell lines of these tumor types characterized by translocations involving the chromosomal segment 12q13-q15. The results reveal that for nearly all tumors and cell lines analyzed, the chromosome 12 breakpoints map within a 350-kb region included in ULCR12, despite the previous cytogenetic assignment of the breakpoints to different bands of that region.

Description of a novel fusion transcript between HMGI-C, a gene encoding for a member of the high mobility group proteins, and the mitochondrial aldehyde dehydrogenase gene.

Aberrations involving the chromosomal region 12q24 are a nonrandom cytogenetic abnormality in frequent benign tumors mainly of mesenchymal origin, e.g., uterine leiomyomas, pleomorphic adenomas of the salivary gland, lipomas, or hamartomas of the lung.

Malignant progression of an HPV16-immortalized human keratinocyte cell line (HPKIA) in vitro.

The DNA of human papillomavirus (HPV) types found in cervical carcinomas can immortalize primary human keratinocytes. However, in analogy to tumor progression in vivo, HPV-immortalized keratinocytes require secondary events for malignant conversion. Here, we report on an HPV16-immortalized keratinocyte cell line (HPKIA) which after gamma-irradiation and long term culturing in vitro has acquired the ability to form squamous cell carcinomas in nude mice.

A 6-Mb yeast artificial chromosome contig and long-range physical map encompassing the region on chromosome 12q15 frequently rearranged in a variety of benign solid tumors.

Cytogenetic analysis of a variety of benign solid tumors, among which uterine leiomyoma, lipoma, pleomorphic salivary gland adenoma, and pulmonary chondroid hamartoma, has indicated that these tumors often display chromosome breakpoints in region q13-q15 of chromosome 12. In previous studies, we have reported that these breakpoints map between locus D12S8 and the CHOP gene, the latter of which has been shown to be consistently rearranged in myxoid liposarcomas with t(12;16)(q13;p11). Here, we report directional chromosome walking studies starting from D12S8 and resulting in the construction of a YAC contig of about 6 Mb.

A hamartoma of the breast with an aberration of 12q mapped to the MAR region by fluorescence in situ hybridization.

Cytogenetic studies of a breast adenolipoma (hamartoma) of a 58-year-old patient revealed a karyotype 46,XX,add(4)(?),add(6)(q?),der(7)t(7;12)(q11.1 or q11.2;q11 or q12),der(12).

Selective loss of integrated Epstein-Barr virus genomes after long-term cultivation of Burkitt's lymphoma x B-lymphoblastoid cell hybrids due to chromatin instability at the integration site.

Independently established somatic cell hybrid clones between the Burkitt's lymphoma (BL) cell line BL 60 and the autologous Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell line (LCL) IARC 277 were analyzed with regard to physical state of EBV and karyotype changes in long-term culture. Early after fusion these hybrids carry EBV genomes of the parental BL cell line integrated near the breakpoint of a translocation chromosome der(19) t(11;19) as well as episomal viral DNA molecules of the parental LCL. During long-term culture, however, all hybrid cell lines lost the integrated EBV sequences and retained exclusively episomal EBV, whereas in parental BL cells the EBV genomes remained stably integrated.

Regional fine mapping of the multiple-aberration region involved in uterine leiomyoma, lipoma, and pleomorphic adenoma of the salivary gland to 12q15.

Cytogenetic aberrations involving 12q13-15 are frequently observed in a variety of benign solid tumors. Using a chromosome walking approach combined with fluorescence in situ hybridization analysis, we were able to show that the chromosome 12 breakpoints involved in uterine leiomyoma, pleomorphic adenoma of the salivary gland, and lipoma cluster to the same chromosomal region, which we therefore designated MAR (multiple-aberration region). By comparing the G-banding pattern of prometaphase chromosomes of amniotic fluid cells and lymphocytes to the position of hybridization signals obtained with a cosmid pool encompassing this breakpoint hot spot region, MAR was assigned to 12q15.

Cytogenic and molecular analysis of an aggressive angiomyxoma.

Aggressive angiomyxoma is a rare mesenchymal tumor occurring mainly in the vulvar region extending into the paravaginal and perirectal region. Histologically, this tumor is rich in vascular structures and in collagen fibers and is of myxoid appearance. Cytogenetic and molecular analysis was performed on a case of an aggressive angiomyxoma and revealed clonal karyotypic abnormalities.

Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours.

We recently showed that the 1.7 megabase multiple aberration region (MAR) on human chromosome 12q15 harbours recurrent breakpoints frequently found in a variety of benign solid tumours. We now report a candidate gene within MAR suspected to be of pathogenetical relevance.

Molecular characterization of 12q14-15 rearrangements in three pulmonary chondroid hamartomas.

Chromosomal aberrations involving the chromosomal breakpoint region 12q14-15 are frequently seen in a variety of mesenchymal tumors as uterine leiomyomas, lipomas, myxoid liposarcomas, enchondromas, or hemangiopericytomas. Therefore, this breakpoint region seems to be one of the most frequent chromosomal abnormality associated with the initiation of human mesenchymal neoplasms. To narrow down the breakpoint region on a molecular level in cells of three pulmonary chondroid hamartomas with 12q14-15 aberrations, we performed fluorescence in situ hybridization analysis with different cosmid clones originating from a YAC and cosmid contig overspanning parts of the region 12q14-15.