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Biomedical subjects

J Mark

Publications and source records attributed to J Mark.

At least 73 records · Page 4Linked to original sources

Chromosome studies in thyroid neoplasia.

Cytogenetic studies in thyroid neoplasia were performed by G-banding of chromosome preparations obtained from the in vitro cultures of nine adenomas, one follicular carcinoma, five papillary carcinomas, and two medullary carcinomas. Complex structural chromosome aberrations were found in one adenoma. Two more adenomas, both composed of Hürthle cells, showed multiple numerical chromosome deviations with trisomy 4 and tetrasomy 7 in common. Six metastasizing carcinomas were characterized by normal stemlines, which indicates that malignancy in thyroid neoplasia cannot be excluded by cytogenetic techniques used currently. Comparisons between cytogenetic findings and cytophotometric DNA measurements in the material studied illustrate that euploid tumors represent a heterogenous group including cases with various gross structural chromosome aberrations of yet unknown clinical significance. Further studies of additional material with long-term follow-up are called for by our findings of structural and numerical chromosome aberrations in follicular neoplasms that are benign according to histologic criteria.

Adenoma↗

Chromosomal composition of malignant human gliomas through serial subcutaneous transplantation in athymic mice.

The karyotypes of seven human glioblastomas were followed through serial subcutaneous passage in athymic mice. One tumor maintained the same hypodiploid stemline as seen in the original biopsy. Three tumors that originally had near-diploid stemlines showed an increase in stemline number to pseudodiploid or hyperdiploid due to gains of whole chromosomes. One tumor showed an entirely different karyotypic profile in the xenograft than had been demonstrated originally. Two tumors showed a shift from near-diploid stemlines to near-tetraploid and near-pentaploid stemlines. Structural abnormalities, including double minutes, that were present originally were maintained in the xenografts, and acquisition of new marker types was rare. Five of the seven lines showed an increased growth rate with serial passage as measured by a shortening of tumor doubling time and decreased time to 1000-mg size. There was, however, no obvious relationship between this change in growth rate and the karyotypic or histologic pattern. These studies demonstrate that most subcutaneous xenografts derived from malignant human gliomas retain karyotypes similar to those seen originally, making these systems useful models for studying the biologic significance of the chromosomal abnormalities of these tumors.

Animals↗

High p21RAS expression levels correlate with chromosome 8 rearrangements in benign human mixed salivary gland tumors.

The expression of RAS oncogenes in benign and malignant salivary gland tumors was studied by immunohistochemistry and by immunoblotting using monoclonal antibodies recognizing the HRAS and KRAS gene products. Twenty-eight out of 29 benign pleomorphic adenomas overexpressed p21RAS, whereas only 12 out of 18 malignant salivary gland tumors expressed the p21 protein. The expression levels were also substantially higher in the adenomas than in the malignant tumors, indicating that RAS gene activation appears to be more frequent and of greater importance for benign than for malignant salivary gland tumors. Comparisons of the p21 expression levels with the karyotypes of the pleomorphic adenomas revealed a novel correlation between high p21 expression and chromosome 8 rearrangements. As a hypothesis, it is suggested that a novel gene located on the proximal long arm of chromosome 8, most likely at band q12, is involved in the regulation of RAS gene expression.

Adenoma, Pleomorphic↗

Cytogenetic relationship between uterine lipoleiomyomas and typical leiomyomas.

The chromosomes from two human uterine lipoleiomyomas, L25 and L26, from the same patient, were studied by a banding technique applied to preparations from short-term cultures. Both tumors displayed the same pseudodiploid stemline characterized by the reciprocal translocation t (5; 12) (q12; q24). These observations coincide with the previous finding that the largest subgroup of typical leiomyomas with an abnormal stemline are characterized by a long-arm change of one chromosome No. 12. The combined results support the previously advanced hypothesis that different histologic subtypes of uterine leiomyomas are derived from a common totipotential stem cell. This interpretation also fits with a proposed theory about the derivation of malignant leiomyomatous uterine neoplasms.

Female↗

Cytogenetic observations in a human gastric leiomyosarcoma.

The chromosomes of a human gastric leiomyosarcoma were studied in preparations from short-term cultures. The tumor had a triploid-near-triploid modal population characterized by extensive numerical and structural changes. Of these deviations, del(1)(p12-13), monosomy 14, and underrepresentation of chromosomes 18 and 22 were abnormalities in common with two of the three previously studied leiomyosarcomas of the small bowel.

Chromosome Aberrations↗

Specificity of asbestos-induced chromosomal aberrations in short-term cultured human mesothelial cells.

Short-term cultured normal human mesothelial cells were exposed for 48 hours to three different asbestos compounds, crocidiolite, chrysotile, and amosite. In the concentration used (0.01 mg/ml) all three asbestiform minerals caused, within a few days, a significant increase of cells showing numerical and/or structural abnormalities. The abnormalities were analyzed in detail using banding techniques. The results were compared with the cytogenetic observations in 52 published cases of mesotheliomas. This comparison revealed only a few similarities as regards numerical deviations. The structural rearrangements in asbestos-exposed cultures, however, in many instances involved chromosome types and chromosome regions preferentially affected in mesotheliomas.

Asbestos↗

Partial 6q deletion in a human salivary gland adenocarcinoma.

G-banding analysis was performed on a cultured human salivary gland adenocarcinoma. Clonal chromosome abnormalities consisted of a 6q- marker and loss of the Y chromosome. The 6q- marker had resulted from a long arm interstitial deletion, del(6)(q22q24). The present results, together with our previous findings of 6q deletions in other types of salivary gland tumors, indicate that deletions of 6q are characteristic for the karyotypic evolution of all major types of malignant salivary gland tumors. A common pathogenetic mechanism for these tumors might well be loss of a tumor suppressor gene located on 6q.

Adenocarcinoma↗

Karyotypic evolution in a human mucoepidermoid carcinoma.

Chromosomes were studied in cultured material from two different areas of a human mucoepidermoid carcinoma. The detailed banding analyses showed no less than 41 different karyotypes. Comparisons between these revealed (1) that the tumour probably had originated with a normal, diploid stemline; (2) that the progression had mainly proceeded by steps in a hyperdiploid direction, by, as a rule, sequential numerical deviations; and (3) that there existed at least eight further, different, evolutionary products from the original stemline. The complex progressional pattern disclosed in the present case contrasts with cytogenetical data documented for most human benign as well as malignant tumour types.

Aged↗

Similar chromosomal evolution in a uterine stromomyosarcoma and in one of two leiomyomas from the same patient.

The chromosomes from three uterine tumours found in the same patient, two benign leiomyomas (L22 and L23) and a low-grade stroma cell sarcoma with leiomyomatous differentiation (L24), were studied by banding technique. L23 had an abnormal stemline distinguished by triosomy 12. The sarcoma showed a stemline with the same 7q-marker as L23 plus a marker del (12)(q13-24). A comparison with cytogenetically studied myomas collected from the literature showed (1) that there are at least three different recurrent, primary, gross chromosomal changes, viz. t(12;14)(q14-15;q23-24), t(1;2)(p36;p24) and del(7)(q22-31) and that there exist at least five further types of primary chromosomal deviations. The sarcoma showed aberrations identical or closely related to the recurrent structural deviations in myomas. These observations indicate a similar evolutionary pattern in benign and malignant leiomyomatous tumours.

Chromosome Aberrations↗

Origin and relationship between different cell types in malignant fibrous histiocytoma.

The derivation of histiocyte-like cells in malignant fibrous histiocytoma (MFH) has been a matter of debate. To shed light on this problem two cell lines from two subsequent recurrencies of MFH were established. The existence of two different cell populations, mainly fibroblast-like in the first cell line and mainly histiocyte-like in the second, was shown by light and electron microscopy, DNA measurements, and karyotype analysis. By detailed banding analysis and identification of several identical chromosomal marker types in the two cell lines, it was proven that they originally derived from the same single cell or single clone. Because the first cell line, with mainly fibroblast-like cells, was in the hypotriploid region and the second, with mainly histiocyte-like cells, was in the penta-hexaploid region, the data explained the appearance of histiocyte-like cells in MFH as a consequence of chromosomal progression.

Aged↗

Significance of the choice of tissue culture technique on the chromosomal patterns in human mixed salivary gland tumors.

Cytogenetic observations by banding methods in 56 new cases of human benign pleomorphic adenomas are reported. Thirty of the cases (series I) were studied in preparations from primary cultures established from cells growing out from mechanically dispersed tumor pieces. The remaining 26 cases (series II) were analyzed in preparations from primary cultures established from enzymatically pretreated material. The use of the latter method resulted in a decrease in the frequency of cases with a normal stemline from about 53% to about 19%. However, the general characteristics of the aberrations observed in abnormal stemlines in both series agreed well. The minor differences observed consisted of a higher frequency of recurrent t(3;8)(p21;q12) in series II and, in the same series, fewer cases showing an involvement of 8q or 12q. The present results emphasize the importance of molecular studies of, in particular, the regions 8q12, 12q13-15, and 3p21.

Adenoma, Pleomorphic↗

Specific chromosomal abnormalities in malignant human gliomas.

Karyotypic analysis of 54 malignant human gliomas (5 anaplastic astrocytomas, 43 glioblastoma multiformes, 3 gliosarcomas, 2 giant cell glioblastomas, 1 anaplastic mixed glioma) has demonstrated that 12 tumors contained normal stemlines or only lacked one sex chromosome. The 42 tumors with abnormal karyotypes included 38 tumors which could be completely analyzed. Six of these 38 cases had near-triploid or near-tetraploid stemlines and 32 had near-diploid stemlines. Statistically significant numerical deviations in the near-diploid group were gains of chromosome 7 (26 of 32; P less than 0.001), and losses of chromosome 10 (19 of 32; P less than 0.001). Double minutes occurred in 18 of 32 near diploid tumors. The distribution of structural abnormalities was analyzed statistically by comparing the incidence of breakpoint in each chromosomal arm to the expected value based on chromosomal arm length. This analysis demonstrated that structural abnormalities of 9p and 19q were significant statistically (P less than 0.005 and P = 0.02, respectively). Although chromosome 1, 6p, the centromeric region of chromosome 11, 13q, and 15q were also frequently involved in structural abnormalities, the incidence of these breaks did not reach statistical significance. This demonstration of specific chromosomal abnormalities in near-diploid gliomas provides the basis for the investigation of genes which may be quantitatively or qualitatively altered in these neoplasms.

Adult↗

Structural chromosomal abnormalities in human medulloblastoma.

Seven human medulloblastomas (four primary cerebellar, three recurrent or metastatic) were karyotyped in direct preparation and/or short-term or early culture. One tumor had a 46,XX stem line. Four of the six remaining tumors contained one or more i(17q), and three of these six tumors had deletions of extra copies of chromosome #1, resulting in trisomy of 1p, 1q, or both. Two tumors had near-centromeric breaks of chromosome #3, two tumors contained unbalanced translocations with breakpoints at 20q13, and two tumors contained double minutes. These findings suggest that the primary karyotypic deviations of human medulloblastomas are gains of whole chromosomes, which are then either deleted or involved in unbalanced translocations, resulting in partial trisomies.

Adolescent↗