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Biomedical subjects

N Mandahl

Publications and source records attributed to N Mandahl.

At least 271 records · Page 15Linked to original sources

A squamous cell bladder carcinoma with karyotypic abnormalities reminiscent of transitional cell carcinoma.

A squamous cell carcinoma was investigated cytogenetically by means of chromosome banding. The karyotype was complex with many structural and numerical changes, including -9 and del(11p), aberrations that also have been noted in transitional cell carcinoma. Thus, cytogenetic studies may be an important complement to the histological classification of bladder tumors, and may even contribute to our understanding of the etiology and pathogenesis of the 2 main types of bladder cancer.

Aged↗

Constitutional C-band polymorphism in lymphocytes from patients with chronic myeloid leukemia.

The C-band heterochromatin polymorphism of chromosomes 1, 9, and 16 was studied in lymphocytes from 53 patients with Ph1-positive chronic myeloid leukemia (CML) and 183 control persons. The patients had significantly larger heterochromatic blocks on chromosome 16 (p less than 0.01) and fewer partial inversions of chromosome 9 (p less than 0.05) than the control persons, whereas no differences were found for the symmetry/asymmetry pattern. We suggest that the increased constitutive heterochromatin regions may, via sister chromosome exchange, facilitate homo- or hemizygotization of genes which favor neoplasia development and/or progression.

Chromosome Aberrations↗

In situ hybridization localizes the human type II alpha 1 collagen gene (COL2A1) to 12q13.

We have, using in situ hybridization technique, localized the human type II alpha 1 collagen gene (COL2A1) to chromosome band 12q13. The gene had previously been assigned to either 12q13.1-13.2 or 12q14.3. Since the chromosome segment 12q13-15 has been shown to be rearranged in several benign and malignant human neoplasms, the exact band localization of COL2A1 within this region makes it a useful marker for the molecular analysis of these tumors.

Chromosome Mapping↗

No abnormal C-band polymorphism in lung cancer patients.

The C-band heterochromatin polymorphism of chromosomes 1, 9, and 16 was studied in lymphocytes from 52 lung cancer patients and 183 control persons. No significant differences between the controls and patients were found regarding heterochromatin block size, the frequency of partial and total inversions, or the symmetry/asymmetry pattern.

Chromosome Banding↗

Genetic convergence during serial in vitro passage of a polyclonal squamous cell carcinoma.

A cell line was established from an in situ squamous cell carcinoma of the skin (Bowen's disease), and its in vitro karyotypic evolution was cytogenetically analyzed. Initially, considerable genetic heterogeneity was evident. Nine cytogenetically abnormal clones, eight of which were apparently unrelated, were found among the 83 metaphases analyzed from the primary culture and the first passage. With increasing time in culture this complexity was reduced, so that a single clone dominated passages 7-11. The clone that emerged from this genetic convergence had a t(12;17)(p13;q21) as the sole abnormality. Our findings indicate that the cytogenetic multiclonality that has been repeatedly detected in short-term cultures of squamous cell carcinomas is not caused by the in vitro conditions. Instead, the principles of Darwinian selection apply: the altered, but stable, selection pressure facing a newly established and initially multiclonal cell line will lead to a reduction of genetic heterogeneity until the one clone that now has the proliferative advantage outgrows the other subpopulations.

Biological Evolution↗

Trisomy 7 and sex chromosome loss in human brain tissue.

Short-term cultures of nonneoplastic brain tissue from 11 patients, seven of whom had a malignant brain tumor, were cytogenetically examined. In only a single case was a wholly normal chromosome complement detected; the remaining ten cases exhibited mosaicism with clonal numerical aberrations found alongside cells carrying a normal karyotype. The abnormal clones were characterized by trisomy 7, the loss of the Y chromosome in men and an X chromosome in women, or by combinations thereof. No structural aberrations were present. Our findings demonstrate that although -Y, -X, and +7 have in the past repeatedly been associated with brain tumors, these changes presumably reflect normal in vivo organ mosaicism and, thus, should not be accepted as neoplasia-specific in this context.

Adult↗

Different karyotypic features characterize different clinico-pathologic subgroups of benign lipogenic tumors.

On the basis of the cytogenetic analysis of tumor cells from a total of 50 lipomas, we conclude that 4 main cytogenetic subtypes may be recognized: (1) tumors with normal karyotype (18 cases); (2) tumors with rearrangements of 12q13-14 (18 cases); (3) tumors with ring chromosomes (6 cases); (4) tumors with other clonal changes (8 cases). This karyotypic heterogeneity parallels other disease characteristics in the following manner: all 6 tumors containing ring marker chromosomes were histopathologically classified as atypical lipomas (6 of the 50 tumors were diagnosed as atypical) or (in 2 cases) lipomas with foci of atypia. In only one single solitary lipoma with focal atypia were no ring chromosomes detected in the tumor cells. This contrasts strongly with the findings in typical solitary lipomas, where rings were found in only 2 of 37 tumors, or, if the 3 tumors with focal atypia are excluded, in none of 34. Furthermore, all 7 multiple lipomas were karyotypically normal, whereas among solitary tumors the corresponding proportion was 11 of 43. We conclude that ring marker chromosomes may be a distinguishing cytogenetic feature of atypical lipomas, and that multiple lipomas, in contrast to their solitary counterparts, are karyotypically normal. These findings emphasize that different tumorigenic pathways are likely to be involved in different groups of benign lipogenic neoplasms.

Adult↗

Multiple karyotypic abnormalities, including structural rearrangements of 11p, in cell lines from malignant melanomas.

Cell lines were obtained from three malignant melanoma patients by culturing cell suspensions from tumor biopsies. A total of six lines (I to VI) were established. One line each was established from the first two cases. Lines III and IV were established from two different methyl cellulose colonies derived from the primary tumor of case 3; line III was from a non-pigmented and line IV from a pigmented colony. Cloning of line IV resulted in two highly malignant (IV Cl 1 and IV Cl 3) and one less malignant (IV Cl 2) clone. Clone IV Cl 1 was inoculated intracardially in nude mice and gave rise to adrenal and brain metastases. Lines V and VI were derived from such metastases. Multiple structural and/or numerical chromosome abnormalities were detected in all lines. Line I had 57-61 chromosomes, with structural changes affecting 1p, 2p, 3q, 7p, 7q, 11p, 14q, 17q, and 22q, as well as one unidentified marker. Line II had 40-48 chromosomes, with structural changes of 1p, 1q, 4q, 5p, 6p, 8p, 11p, 11q, 14p, 20p, and two unidentified markers. Line III had 45 chromosomes, 6q+, del(11p), and a centric fusion between chromosomes 14 and 15. Line IV had 45-46 chromosomes. The clonal changes included rearrangements of 1p, 9p, 11p, and the centric fusion of chromosomes 14 and 15. Line V was pseudodiploid and contained aberrations of 1p, 9p, 11p, 14q, 20q, an isochromosome for 21q, and an unidentified marker. Finally, the pseudodiploid line VI had changes of 9p, 11p, centric fusion of chromosomes 14 and 15, and an unidentified marker. Although no single identical aberration was shared by all six lines, structural abnormalities of 11p were invariably present and, hence, might constitute a common cytogenetic feature in melanoma development. The most consistent difference between the amelanotic and melanotic lines derived from case 3 was the presence of a 6q+ marker in the former and a 9p+ marker in the latter.

Chromosome Aberrations↗

Multiple structural chromosome rearrangements, including del(7q) and del(10q), in an adenocarcinoma of the prostate.

Cytogenetic analysis of a poorly differentiated adenocarcinoma of the prostate revealed the complex karyotype: 76-86,X, -Y, +X, +X, +del(X)(q24), +t(1;10) (p22;q24), -2, +der(2) t(1;2;?)(p32;q24p13;?), +der(2)t(1;2;?) (p32;dq24p13;?), +3, +3, +4, +5, +5, +6, +7, +del(7) (q22), -8, +der(8)t(8;?)(q24;?), + der(8)t(8;?)(q24;?), +9, +10, +10, +der(10)t (1;10)(q24;q22), +del (10)(q23), +11, +11, +12, +der(12)t(4;12)(q11;p11), +der(12)t(4;12) (q11;p11), +14, +der (15)t(1;15)(q21;p11), +t(16;?) (q21;?), +17, +18, +19, +19, +20, +20, +21, +22, +2-5 mar. The karyotype contains deletions of both 7q and 10q, abnormalities that also have been described previously in prostatic adenocarcinomas, and which hence may represent primary chromosomal rearrangements in this type of cancer.

Adenocarcinoma↗

Normal frequency of chromosome breakage in lymphocytes from patients with musculoskeletal sarcoma.

Spontaneous chromosome aberrations were studied in lymphocytes from 23 untreated patients with musculoskeletal sarcoma and 27 controls. Among the sarcoma patients, the mean gap, break, and gap + break events per 100 metaphases were 0.9, 2.2, and 3.0, respectively. The corresponding values for the control group were 1.3, 1.6, and 2.8. The mean number of aberrant mitoses was 2.4% in the sarcoma group and 2.5% in the controls. None of the differences between patients and controls were statistically significant. Thus, we found no evidence of inherent chromosome instability in patients with malignant mesenchymal tumors.

Adolescent↗

Isochromosomes i(8q) or i(9q) in three adenocarcinomas of the lung.

We have cytogenetically analyzed three primary adenocarcinomas of the lung. All tumors had chromosome numbers in the triploid region. The multiple structural aberrations included rearrangements of 3p, in two cases affecting the segment 3p14-23, where deletions are characteristically found in small cell lung carcinomas. Isochromosomes for 8q were present in two tumors and i(9q) in one tumor. In the few previously reported cytogenetic analyses of pulmonary adenocarcinomas, all of which examined metastases or cell lines, i(8q) was found in one case and i(9q) in two cases. These isochromosomes, therefore, represent previously unrecognized nonrandom changes in adenocarcinomas of the lung, and might constitute primary aberrations in this tumor type.

Adenocarcinoma↗

Bands involved in primary chromosome rearrangements in sarcomas are not constitutionally liable to breakage in sarcoma patients.

The localization of breakpoints in spontaneous chromosome aberrations, i.e., chromatid and chromosome gaps, breaks, and exchanges, has been studied in cultured skin fibroblasts from 34 untreated patients with musculoskeletal sarcoma and 38 controls. A total of 325 aberrations in the sarcoma group and 251 in the control group could be assigned to particular bands. The distribution was non-random (P less than 0.001) in both groups. Twenty-one bands in the sarcoma group and 20 in the control group appeared as hot spots, with 11 represented in both groups. Only three hot spots, all of which were present among both patients and controls, coincided with bands involved in primary sarcoma-associated chromosome rearrangements. The results indicate that the chromosome breakage pattern of non-malignant cells is similar in sarcoma patients and controls. Hence, the occurrence of primary structural rearrangements in sarcomas cannot be accounted for by any constitutional proneness to chromosome breakage at these bands.

Adult↗

Three major cytogenetic subgroups can be identified among chromosomally abnormal solitary lipomas.

We have investigated cytogenetically a total of 35 solitary lipomas, 10 of which have been reported previously. Of the 25 tumours presented herein for the first time, clonal chromosome aberrations were detected in 17. The remaining eight had normal karyotypes, although two of them had nonclonal aberrations in about one quarter of the cells. Based on the cytogenetic findings in all 35 lipomas, four major subgroups can be distinguished. These are characterized by: (I) hyperdiploid karyotypes including one or more supernumerary ring chromosomes (5 cases); (II) diploid karyotypes with mostly balanced rearrangements involving 12q13-14 (13 cases), including the rearrangement t(3;12) (q27-28;q13-14) in 4 cases; (III) hypodiploid or diploid karyotypes with other aberrations than ring chromosomes or rearrangements of 12q13-14 (8 cases); and (IV) normal karyotypes (9 cases).

Adult↗

Rings, dicentrics, and telomeric association in histiocytomas.

We report clonal karyotypic abnormalities in six of 12 cytogenetically investigated malignant fibrous histiocytomas. Four of eight tumors of the pleomorphic subtype had complex clonal chromosome aberrations, including ring chromosomes, dicentric chromosomes, and/or telomeric associations. No common characteristic aberration could be distinguished. Two of four myxoid tumors had clonal changes: One had one to two ring chromosomes and an extra chromosome #2; another had a supernumerary ring chromosome as the sole abnormality.

Aged↗

Unique karyotypic abnormalities in a squamous cell carcinoma of the larynx.

We have cytogenetically examined short-term cultures from a squamous cell carcinoma of the larynx, a type of carcinoma in which chromosome aberrations have hitherto not been reported. The tumor karyotype was 46,XY,inv(2)(p22q24),t(9;13)(q34;q12),t(11;18)(q23;q21). None of these abnormalities have been described in carcinomas before.

Aged↗

Multiple unrelated clonal chromosome abnormalities in an in situ squamous cell carcinoma of the skin.

We have cytogenetically analyzed short-term cultures from an in situ squamous cell carcinoma of the skin (Bowen's disease). The following mosaic tumor karyotype was found: 46,XX, -1, +der(1)(pter----p22::q11----cen----p22:), -9, +der(9)t(1;9)(q11; p24)/46,XX,t(3;6) (q21;p21)/46,XX,t(5;14)(q13;q24),t(7;18)(q32;q11)/46,XX,t(8;11)(p22;q13) /46, XX,t(8;11) (p22;q13),t(15;17) (q13;q24)/46,XX,t(12;15)(q12;p11). None of the rearrangements correspond to previously known cancer-associated abnormalities. Two of the clones are obviously related, and it is reasonable to assume that the t(15;17) developed as an evolutionary change in a cell that already contained t(8;11)(p22;q13). Since five clones without cytogenetic similarities were found in this in situ skin carcinoma, we suggest that the tumor was of polyclonal origin. It is impossible to decide whether all, or indeed any, of the visible abnormalities constitute pathogenetically essential primary changes, or merely represent chromosomal markers of secondary importance in tumorigenesis.

Carcinoma in Situ↗

Trisomy 5 and t(5;14)(q11;q32) as the sole abnormalities in two different clones from a centroblastic non-Hodgkin's lymphoma.

A 62-year-old previously healthy woman presented with a centroblastic non-Hodgkin's lymphoma in the thyroid. Chromosome analysis revealed two unrelated clones, 47,XX,+5 and 46,XX,-14,+der(14)t(5;14)(q11;q32). The two clones may reflect a polyclonal origin, or they may be the descendants of the same neoplastically rearranged cell. In the latter case, the clonal aberrations are either secondary to an event detectable only at the molecular level, or one of them is a primary cytogenetic event while the other arose through clonal evolution with loss of the primary aberration. The best candidate for the primary change would be trisomy 5. Trisomy 5 has previously been associated with lymphomas with diffuse, large, noncleaved morphology, a group within the Working Formulation largely equivalent to centroblastic lymphomas in the Kiel classification. Our findings thus support the notion that trisomy 5 may be associated with centroblastic/diffuse, large, noncleaved lymphomas.

Chromosome Banding↗