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Biomedical subjects

F Mitelman

Publications and source records attributed to F Mitelman.

At least 307 records · Page 17Linked to original sources
PubMed1989

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↗
PubMed1989

Primary chromosome abnormalities in human neoplasia.

At the cellular level, cancer is a genetic disease; genetic changes in somatic cells are essential events in neoplasia. In a majority of cases these changes involve large enough blocks of genetic material to be visible in the microscope. The chromosome aberrations in neoplastic disorders are probably of three kinds: (1) primary abnormalities, which are essential steps in establishing the tumor; (2) secondary abnormalities, which develop only after the tumor has developed, but which nevertheless may be important in tumor progression; and (3) cytogenetic noise, which is the background level of nonconsequential aberrations. These latter changes are, in contrast to the primary and secondary changes, randomly distributed throughout the genome. The primary abnormalities, of which several dozens have now been identified, are mostly strictly correlated with particular diseases and even with histopathological subtypes within a given disease. This has been evident in the leukemias for some years already, and information now accumulating on solid tumor karyology indicates a similar situation. Clonal chromosome abnormalities are a feature of both benign and malignant neoplasms, although the changes are often less massive in the former. Apart from being clinically useful as a diagnostic technique and an aid in prognostication, tumor cytogenetics also plays a role in identifying those genomic sites which harbor genes essential in the pathogenesis of neoplastic lesions. So far, two functionally different classes of directly cancer-relevant genes have been detected, the oncogenes and antioncogenes. There is every reason to believe that future investigations with cytogenetic and recombinant DNA methods will add to our knowledge of the biology of human neoplasia, in those tumor types where the characteristic genetic change is already partially known, and by identifying hitherto unknown karyotypic abnormalities.

Chromosome Aberrations↗
PubMed1989

Relation between occupational exposure to organic solvents and chromosome aberrations in non-Hodgkin's lymphoma.

Chromosome analysis of lymphoma cells was performed in 54 untreated patients with non-Hodgkin's lymphoma (NHL). 10 patients had a history of daily occupational handling of organic solvents for at least 1 year (exposed group) and 44 patients had never (or only for shorter periods) worked with solvents (unexposed group). There were no differences between exposed and unexposed patients regarding age, clinical stage or histologic malignancy grade. The patients were assigned to three categories: Patients with 0-4, 5-9, or greater than or equal to 10 cytogenetic events producing clonal aberrations of the lymphoma cells. The proportions of exposed patients in these categories were 2/26 (8%), 5/20 (25%) and 3/8 (38%); respectively, i.e. with increasing numbers of events there was an increasing probability of previous exposure to solvents (p = 0.035, trend analysis). 5 of 7 exposed patients (71%) with intermediate or high-grade lymphomas displayed translocations involving the band 14q32. Such 14q+ markers were found in only 5 out of 28 unexposed patients (18%) with lymphomas of comparable malignancy grade (p = 0.01). Among unexposed patients with intermediate or high-grade lymphoma the most common clonal aberration was 6q- which occurred in 10 out of 28 patients (36%). This abnormality was not observed in the exposed patients with lymphomas of corresponding malignancy grades (p = 0.08). It thus appears that the number of clonal chromosome aberrations is especially large in NHL patients with a history of occupational exposure to organic solvents. Moreover, such exposure may be associated with characteristic cytogenetic changes in the lymphoma cells.

Adult↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Localization in man of fifteen DNA sequences within the chromosome segment 13q12-q22.

Fifteen human chromosome 13 specific DNA fragments, isolated from a lambda phage genomic library, were localized within the segment 13q12-q22. One was mapped to 13q12.1-q12.2, three to 13q12.3-q13.1, one to 13q14,1-q14.2, five to 13q14.1-q21.1, one to 13q21.1-q21.2, two to 13q21.2, and one to 13q22.1, and one to 13q22. The localization was performed by hybridization to Southern blots of a panel of human cell lines with overlapping deletions in 13q, and for three probes also by in situ hybridization to metaphase chromosomes.

Cell Line↗
PubMed1989

Report of the committee on structural chromosome changes in neoplasia.

An enormous amount of data on neoplasia-associated chromosome aberrations has accumulated over the past two years. More than 4,000 tumors with a chromosome anomaly identified by banding have been published since HGM9, and the total number of cases contained in the registry on which the Catalog of Chromosome Aberrations in Cancer (Mitelman, 1988) is based is now well above 12,000. The information presently available is, however, still in many respects incomplete. First, the data is heavily biased in favor of hematologic disorders. Solid tumors comprise only 20% of the total data base, which is totally disproportionate to the relative contribution of these disorders to human cancer morbidity and mortality. For example, malignant epithelial tumors (carcinomas), which cause almost 80% of all cancer deaths in man, comprise only 7% of the total. Second, our knowledge about early stage tumors is very limited. For example, the great majority of the solid tumors that have been studied cytogenetically have been metastatic lesions or effusions (advanced tumors usually have a large number of complex structural and numerical chromosome aberrations). Obviously, many more such neoplasms will have to be studied before the primary (pathogenetically essential) changes can be distinguished from the confusing variety of secondary abnormalities that may dominate the karyotype. It should be noted that secondary changes may also be nonrandom, and may be important for tumor progression. Therefore, no attempt has been made in this report to distinguish between primary and secondary changes. All nonrandomly occurring abnormalities that met the criteria for inclusion are listed in Table 1 irrespective of their presumed pathogenetic significance. Results of molecular genetic studies (e.g. the demonstration of loss of heterozygosity or gene amplification) were not considered, although they may be included in the HGM10.5 report. A total of 149 nonrandom chromosome changes were identified (Table 1) in 43 different types of neoplastic disorders, including hematologic diseases and malignant lymphomas, as well as tumors of epithelial, mesenchymal, neurogenic, germ cell, and melanocytic origin. The aberrations comprise a variety of structural chromosome rearrangements (translocations, inversions, insertions, deletions, duplications and isochromosomes), and all chromosomes, except the Y chromosome are involved. The great majority (121 of the 149 identified aberrations) represent well-defined, specific structural changes. More than half of them are consistently associated with a particular morphologic disease characteristic. Twenty-eight of the aberrations, although nonrandom, are not characterized as well. Most are deletions or translocations that only affect a certain chromosome region, often spanning several bands.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromosome Aberrations↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Cytogenetically unrelated clones in hematological neoplasms.

We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.

Chromosome Aberrations↗
PubMed1988

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↗
PubMed1988

Consistent involvement of only 71 of the 329 chromosomal bands of the human genome in primary neoplasia-associated rearrangements.

In an attempt to quantify the nonrandomness of primary neoplasia-associated acquired chromosomal aberrations in humans, we have retrieved information from a computerized data base on the chromosomal abnormalities of 9069 human neoplasms. By restricting the survey to the 1985 cases with a solitary structural rearrangement, we attempted to limit the analysis to only those aberrations that were most likely to represent pathogenetically important, primary changes. The breakpoints of the primary abnormalities thus identified clustered to 71 bands. It furthermore turned out that 27 of the 41 oncogene sites known with reasonable precision (i.e., localized within one or two bands) coincide with bands consistently involved in neoplasia-associated rearrangements. These comparisons add to the evidence that acquired, cancer-associated chromosomal aberrations are nonrandom in distribution, that only a limited number of genomic sites are consistently involved in primary neoplasia-associated aberrations, and that the concordance between the breakpoints of primary aberrations and the location of cellular oncogenes is greater than predicted by chance.

Chromosome Aberrations↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗