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F Mitelman

Publications and source records attributed to F Mitelman.

At least 199 records · Page 11Linked to original sources
PubMed1993

Aberrations of chromosome segment 12q13-15 characterize a subgroup of hemangiopericytomas.

BACKGROUND: In later years, several characteristic acquired chromosomal aberrations have been identified in mesenchymal tumors. Many of these aberrations, either alone or with histopathologic and clinical data, are useful in diagnosis. The cytogenetic profile of hemangiopericytomas has been poorly investigated. METHODS: Short-term cultures from four spindle cell tumors were cytogenetically analyzed. RESULTS: Clonal acquired chromosome aberrations were found in three of the four tumors: inv(12) (q14q24) in a malignant hemangiopericytoma, a supernumerary der(3)t(3;12) (p21-23;q13-15) in a benign hemangiopericytoma, and t(6;12;19) (p21;q13;p13) in a spindle cell sarcoma that was histologically a malignant hemangiopericytoma or a synovial sarcoma. The fourth tumor, a malignant hemangiopericytoma, had a normal karyotype. The tumors with inv(12) and t(6;12;19) had subclones with trisomy 5 in addition to the structural changes. CONCLUSIONS: The current findings and the literature data indicate that a subgroup of hemangiopericytomas is characterized by rearrangement of chromosome segment 12q13-15.

Adult↗
PubMed1993

Chromosome abnormalities in eighty-three head and neck squamous cell carcinomas: influence of culture conditions on karyotypic pattern.

Short-term cultures from 115 squamous cell carcinomas (SCC) of the head and neck were cytogenetically investigated. Thirty-six of the tumors have been reported previously, whereas 79 are new cases. The material was divided into two series based on the medium used. The 80 tumors of series I were cultured in RPMI 1640 supplemented with fetal calf serum, glutamine, antibiotics, insulin, cholera toxin, and epidermal growth factor. The 35 tumors of series II were cultured in a chemically defined, serum-free medium with a low calcium concentration, MCDB 153, which stimulates epithelial growth while inhibiting fibroblasts. A total of 83 tumors with clonal karyotypic abnormalities were detected in the two series. Series II had a higher proportion of tumors with complex karyotypic changes than series I (43% versus 15%), a lower proportion of tumors with pseudo- or neardiploid clones characterized by simple rearrangements (3% versus 34%), and a lower frequency of unrelated clones (3% versus 24%), indicating that the different culture conditions favored growth of different cell populations. Except for rearrangements of 1p22, which were mainly found in series I, the distribution of breakpoints in structural aberrations was similar in the two series and clustered to several chromosomal bands or regions, in particular 11q13, 1p22, 1p11-12, 3p11-q11, 5q13, 1q25, 15q10, and 8q10. Unbalanced structural aberrations were more common in series II, frequently leading to loss of segments from chromosome arms 3p, 7q, 8p, 11q, 13p, 14p, and 15p, whereas gain of genetic material often involved chromosome arms 1q, 3q, 8q, and 15q.

Aged↗
PubMed1993

Comparative cytogenetic and DNA flow cytometric analysis of 150 bone and soft-tissue tumors.

Samples from 48 benign and 102 malignant bone and soft-tissue tumors were analyzed cytogenetically and by DNA flow cytometry. Clonal chromosome abnormalities were found in 82 tumors and normal karyotypes in 68; 61 tumors were DNA-non-diploid and 89 were diploid. The cytogenetically abnormal tumors were used for comparison between the 2 types of investigation; 45 of these tumors were DNA-diploid and 37 were DNA-non-diploid. There was, with few exceptions, good correspondence between the quantitative estimates of genomic changes by the 2 methods, indicating that the cells cytogenetically analyzed from short-term cultures are representative of the in vivo cell populations. Discrepancies were primarily found in cases with indexes above 1.5, in which the DNA index was higher than the chromosome index. The chromosome analysis suggested that skewed stemline (G0/G1) peaks in the diploid region in DNA histograms indicate the presence of cell populations with small net quantitative genomic changes, although not all such populations were detected by DNA flow cytometric analysis. The view that one of the peaks in bimodal stemline DNA histograms with narrow peaks represents a non-diploid cell population was also corroborated. On average, the cell populations giving rise to double stemlines in DNA histograms showed quantitatively larger genomic changes than those that gave rise to broad or skewed diploid G0/G1 peaks. The findings indicate that these histogram profiles are not artifactual but reflect chromosomal changes in the tumor parenchyma.

Bone Neoplasms↗
PubMed1993

Cytogenetic aberrations in colorectal adenocarcinomas and their correlation with clinicopathologic features.

BACKGROUND: Little is known about the karyotypes of colorectal carcinomas and, in particular, about how the cytogenetic findings correlate with clinicopathologic features. METHODS: Short-term cultures from 49 colorectal adenocarcinomas were analyzed cytogenetically. The karyotypes were correlated with grade, stage, lymphocytic infiltration, and site (using the chi-square test), with patient age and tumor size (using the Student t test), and with survival (using the log-rank or Mantel-Haenszel test). RESULTS: Normal karyotypes were detected in 17, simple numeric changes in 22, and multiple structural and numeric abnormalities in 10. The most common numeric aberrations were +7, -Y, -18, and -22. The most common structural rearrangements were, in decreasing order of frequency, of chromosomes 1 (eight samples, leading to loss of 1p material in five), 3, 11, 17, 6, 8, 13, and 20. Marked or moderate lymphocytic infiltration was seen significantly less often (P < 0.05) in tumors with complex chromosomal abnormalities than in those with simple anomalies or normal karyotypes. The subset of patients who had tumors with multiple chromosomal abnormalities had a significantly shorter survival time (P < 0.025) than those who had lesions with simple changes or normal karyotypes. CONCLUSIONS: Loss of 1p material is the most consistent chromosomal change in colorectal carcinomas but probably represents a progressional rather than a primary event. Structural changes of chromosomes 3 and 11 seem to be more common in tumors located in the distal part of the large intestine. The significantly shorter survival time of patients with complex aberrations indicates that the karyotype could be used as a prognostic parameter in patients with colorectal cancer.

Adenocarcinoma↗
PubMed1993

Chromosome analysis of 20 breast carcinomas: cytogenetic multiclonality and karyotypic-pathologic correlations.

Short-term cultures from 20 breast carcinomas were analyzed cytogenetically. A normal female chromosome complement was found in 4 cases. Clonal chromosome aberrations were detected in 16 tumors. In 10 tumors, multiple cytogenetic clones were found; in 2 cancers the clones were related, reflecting clonal evolution, but in the remaining 8 tumors the clones were cytogenetically unrelated, indicating clonal heterogeneity in the origin of the tumor parenchyma. Correlation analysis between karyotypic and pathologic parameters indicated that cases with complex karyotypes and/or cytogenetically unrelated clones, when compared with cases with a single simple karyotypic abnormality, were generally of higher histologic malignancy grade, had more mitoses in the histologic sections, and also more often had carcinoma in situ lesions in the same breast.

Aneuploidy↗
PubMed1993

Rearrangement of band q13 on both chromosomes 12 in a periosteal chondroma.

Cytogenetic analysis of a recurrent periosteal chondroma revealed nonreciprocal translocations of both chromosomal segments 12q13-->qter, from one chromosome 12 to 7q32 and from the homologous chromosome 12 to 16q22. The remaining parts of the two chromosomes 12 formed a dicentric chromosome. This is the second reported chondroma with a 12q13-15 rearrangement, and changes of this chromosome region consequently seem to be nonrandom occurrences in chondromas.

Adult↗
PubMed1993

Interstitial deletion of the short arm of chromosome 3 as a primary chromosome abnormality in carcinomas of the breast.

Interstitial deletions of the short arm of chromosome 3 were found in short-term cultures of five breast carcinomas (of 41 breast cancers with clonal aberrations analyzed by us during the same period). They were the only clonal structural change in three tumors; in the remaining two, the clone with 3p-coexisted with seemingly unrelated clones that had other structural and numerical aberrations. The deletions were identical, del(3)(p12p14), in four cases. The fifth tumor seemed to have a smaller deletion, interpreted as del(3)(p13p14). Our findings constitute karyotypic evidence that 3p deletions are relatively common in breast carcinomas and concur with the molecular genetic detection of loss of heterozygosity in this chromosome arm. The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis.

Adenocarcinoma, Mucinous↗
PubMed1993

Trisomy 7 in nonneoplastic cells.

The somatic mutation theory of tumorigenesis states that mutations are necessary for tumor development. On the other hand, acquired, clonal chromosomal alterations are occasionally detected in otherwise normal, nonneoplastic cells--for example, loss of sex chromosomes occurs in bone marrow cells and lymphocytes in elderly individuals--and it is therefore evident that not all mutations are by themselves sufficient for neoplasia to occur. Thus, the finding of an acquired, clonal chromosomal abnormality does not constitute proof that a lesion is neoplastic. Trisomy 7 has, as the sole clonal chromosomal aberrations, been reported in a wide variety of epithelial tumor types but also in some mesenchymal and neurogenic neoplasms. It has been suggested to be a primary, i.e., tumor-initiating, abnormality in tumors of the bladder, brain, colon, kidney, lung, ovary, prostate, and thyroid. But data from cytogenetic studies of solid tumors, macroscopically normal tissue in the proximity of solid tumors, and nonneoplastic lesions now question the importance of a solitary +7 as a neoplasia-associated change. Most solid tumors in which trisomy 7 has been found as the sole change in one clone have also displayed other, cytogenetically unrelated, clones with complex karyotypic abnormalities. Such karyotypic differences among coexisting clones could indicate that the neoplasm is polyclonal, that the cytogenetically disparate clones have emerged during tumor progression from one original clone carrying submicroscopic genomic changes only, or that the clone with +7 does not represent the tumor parenchyma. The latter interpretation is supported by the finding of cells with trisomy 7 in macroscopically normal tissue outside tumors of the brain, kidney, and lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Neoplastic↗
PubMed1993

Chromosome aberrations in tenosynovial giant cell tumors and nontumorous synovial tissue.

Five tenosynovial giant cell tumors--4 pigmented villonodular synovitis (PVNS) and 1 nodular tenosynovitis (NTS)--were investigated cytogenetically. Clonal chromosome aberrations were detected in 3 of them. One PVNS had t(7;16)(q22;q24) as the sole anomaly, whereas 1 PVNS and the NTS displayed aberrations suggesting clonal evolution: t(1;19)(p11;p12)/t(1;19), +12 and ins(5;1)(q31p34)/ins(5;1),t(2;4)(p23;q21), respectively. Including our 3 cases, a total of 6 tenosynovial giant cell tumors with karyotypic changes have been reported. Apart from 2 PVNS with trisomies 5 and 7, and 2 NTS with rearrangement of chromosome band 1p13, no recurrent chromosome change has been detected. Although the detection of clonal, acquired chromosome abnormalities has formerly generally been accepted as sufficient to conclude that a lesion is neoplastic, the interpretation of the pathogenetic significance of the karyotypic aberrations in synovial tumors is obscured by the fact that we have also detected comparable aberrations in obviously nonneoplastic synovial tissue. One of 2 lesions from patients with hemorrhagic synovitis carried a clonal del(13)(q12q21), and 2 of 4 synovectomy samples from patients with rheumatoid arthritis displayed -Y and -Y together with +7. The available cytogenetic data therefore cannot be used to resolve the controversy as to whether tenosynovial giant cell tumors are truly neoplastic or only reactive, inflammatory proliferations.

Adult↗
PubMed1993

Mapping of the 19p13 breakpoint in an ovarian carcinoma between the INSR and TCF3 loci.

Chromosome rearrangements involving band 19p13 have been described in about half of all ovarian carcinomas. Four ovarian carcinomas with translocations of 19p13 were investigated with 11 DNA probes for markers localized to this band. All markers exhibited normal restriction patterns, suggesting that they were not rearranged. The 19p13 breakpoint of one tumor was mapped to a location between the INSR and the TCF3 loci.

Carcinoma↗
PubMed1993

Cytogenetic deletion maps of hematologic neoplasms: circumstantial evidence for tumor suppressor loci.

Research in oncogenetics has led to the identification of two major classes of tumor-associated genes, oncogenes and tumor suppressor genes. In a wide variety of solid tumor types, mutations of both groups of genes have been implicated in the tumorigenic process. In hematologic neoplasms, on the other hand, most attention has focused on illegitimate activation of oncogenes, e.g., deregulation leading to disturbed transcriptional activity and structural rearrangements resulting in hybrid genes. Whether loss or mutational inactivation of tumor suppressor genes also plays an essential role in the genesis of tumors of the hematopoietic system has received less attention. Because such inactivation can be the result of karyotypically detectable loss of chromosomal material, cytogenetic studies may prove helpful in pinpointing genomic sites that harbor tumor suppressor genes. The present study is based on a total of 12,473 cytogenetically abnormal hematologic neoplasms reported in the literature to date. Among these, we selected the 6,422 cases with sole clonal chromosomal abnormalities in order to include only aberrations of importance in the genesis, rather than in the progression, of these neoplasms. All tumors with monosomies or structural abnormalities resulting in loss of chromosomal material were compiled, and for every such structural aberration, i.e., deletion, unbalanced translocation, isochromosome, and ring chromosome, the chromosome bands lost were ascertained. This cytogenetic deletion mapping revealed that the most commonly lost chromosomes were Y and 7 in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloproliferative disorders (MPD); X, Y, 7, 20, and 21 in acute lymphocytic leukemia (ALL); X, Y, and 17 in chronic lymphoproliferative disorders (LPD); and X and Y in non-Hodgkin's lymphoma (NHL). Chromosome segments/bands lost due to unbalanced structural abnormalities in at least 5% of the cases were 5q13-33, 7q22-36, 9q13-31, 11q23-25, 12p12-13, 17p11-13, and 20q11-13 in AML; 5q13-35 and 20q11-13 in MDS; 5q22-23, 7q22, 13q12-22, 17p11-13, and 20q11-13 in MPD; 6q15-27, 9p11-24, 12p12-13, and 19p13 in ALL; 6q16-27, 11q21-25, 13q13-14, and 14q32 in LPD; and 6q21-27, 11q13-25, and 14q24-32 in NHL. Based on these findings, three conclusions can be drawn. First, there is no good correspondence between total and partial monosomies, the only exception being -7 and 7q-, both of which are common in myeloid neoplasms. This indicates different pathogenetic effects of total and partial losses.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromosome Aberrations↗
PubMed1993

Cytogenetic evolution in primary tumors, local recurrences, and pulmonary metastases of two soft tissue sarcomas.

The karyotypic pattern at different stages of tumor development may provide information on tumor progression but few data are available regarding human solid tumors. Cytogenetic analysis was performed on the primary tumor and four lung metastases of a synovial sarcoma, and the primary tumor, two consecutive local recurrences, and six pulmonary metastases, obtained at two different occasions, of a malignant fibrous histiocytoma (MFH). Simultaneous existence of more than one cytogenetically aberrant clone was also assessed through analysis of more than one sample from the same surgical specimen. Clonal chromosome aberrations were detected in all samples from the synovial sarcoma, and in both local recurrences and five of the metastases from the MFH. All clones in both tumors were cytogenetically related. The primary synovial sarcoma tumor contained two clones, one of which was also found in the lung metastases, together with a third clone that had acquired additional aberrations. Four clones with a near-tetraploid chromosome number and complex aberrations were identified in the MFH. Likely evolutionary pathways could be deduced in both cases. In the patient with synovial sarcoma one of the pulmonary metastases, rather than the primary tumor, might well have been the source of another of the pulmonary metastases. In the MFH the cytogenetic findings indicated the presence of two co-existing lineages in the primary tumor, one giving rise to the local recurrences and one to the pulmonary metastases. Our findings show that cytogenetic analysis can be used to establish the chronologic relationships between different clones in primary tumors, local recurrences and distant metastases, to determine what genetic changes are of importance for the metastatic capability of tumor cells, and to help establish the origin of the metastatic lesions.

Chromosome Aberrations↗
PubMed1993

Chromosome aberrations and cytogenetic intratumor heterogeneity in chondrosarcomas.

Clonal chromosome aberrations identified after short-term culture are presented for 13 chondrosarcomas; in 5 cases both the primary tumors and local recurrences were studied. The stemline chromosome number was hypodiploid or hyperhaploid in 9 tumors. The most frequent numerical anomalies were, in falling order of frequency, loss of chromosomes Y, 10, 13, and 6, and gain of chromosomes 7 and 20. No recurrent structural rearrangement was found, but chromosome bands 5q13, 1q21, 7p11, and 20q11 were each involved in three different rearrangements. Karyotypic heterogeneity was assessed in two different ways: as the presence of more than one clone in one sample and as the presence of different clones in different samples from the same surgical specimen. Clonal karyotypic evolution was demonstrated in 6 of the 7 cases in which two or more samples could be investigated. All 6 showed intersample heterogeneity. Intrasample heterogeneity was found in only 5 of the 28 samples with aberrations. By comparing the incidences of the nonrandomly occurring aberrations in stemlines and sidelines in the heterogeneous tumors, it was possible to conclude that loss of chromosome 13 and rearrangement of band 5q13 were early events in the clonal evolution.

Adult↗
PubMed1993

Cytogenetic analysis of six bronchial carcinoids.

Short-term cultures from four typical and two atypical primary bronchial carcinoids were cytogenetically analyzed. A lung metastasis from one of the atypical carcinoids was also analyzed. Of the four typical carcinoids, two had normal chromosome complements, while the other two had the karyotypes 46,X, -X, +7/47,XX, +7/47,XX, +X/46,XX and 47,XX, +7/46,XX. Both atypical carcinoids had chromosome abnormalities. One had the karyotype 45-46,X, -X,del(1)(q32),add(17)(p13), +add(19)(p13), -22, +r/47,XX, +X. The second carcinoid had the karyotype 78-81,XXY, +Y, +1,t(2;8)(q21;q24), +3, +4, +del(4) (q25), +5, +6,der(6)t(6;6)(q21;p21)x2, +7, +7, -10,add(14)(p11-13), +19, -21, +1-4mar. The metastasis from this carcinoid had the same aberrations, except that the del(4)(q25) had been lost and one to two markers had been gained.

Bronchial Neoplasms↗
PubMed1993

Karyotypic abnormalities in tumours of the pancreas.

Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, +20, +7, +11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes 1 (losses in 1p but especially gains of 1q), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours.

Aged↗
PubMed1993

Recombinations of chromosomal bands 6p21 and 14q24 characterise pulmonary hamartomas.

Cytogenetic analysis of short-term cultures from seven pulmonary hamartomas revealed an abnormal karyotype in six of them. The most characteristic aberration was an exchange of material between 6p21 and 14q24, found in three tumours. Abnormalities of either 6p or 14q were seen in another two hamartomas. Other regions that were rearranged more than once were 12q (three times) and 17p (twice), sometimes in exchange with 6p or 14q and giving rise to complex derivative chromosomes. Only one tumour had aberrations that did not involve 6p, 12q, 14q, or 17p. These results-together with the data on three previously reported pulmonary hamartomas, two of which also had t(6;14)-show that recombinations between 6p21 and 14q24 are common, and hence probably pathogenetically important. The data support the view that these tumours are genuine neoplasms rather than developmental anomalies. The coexistence of a common 14q24 breakpoint in uterine leiomyomas and pulmonary hamartomas indicates that a gene important in the genesis of both tumours exists in this band.

Adult↗
PubMed1993

The cytogenetic scenario of chronic myeloid leukemia.

The Philadelphia chromosome (Ph), i.e., the reciprocal translocation t(9;22)(q34;q11), is found with great specificity in bone marrow cells from patients with chronic myeloid leukemia (CML). Variant Ph-producing translocations, seen in 5-10% of all patients, are all complex and involve the same molecular rearrangement as the regular t(9;22). Patients with classic and variant Ph-producing translocations are clinically and hematologically identical, and as a group differ from Ph-negative CML patients. In all patient groups, the occurrence of additional chromosome changes is an ominous sign indicating that disease progression is imminent. The chromosome changes occurring in excess of the Ph in CML are clearly nonrandom and two pathways of cytogenetic evolution may be distinguished. Major route changes comprise trisomy 8, i(17q), trisomy 19, and an extra Ph; totally, 71% of Ph-positive CML patients have at least one of these four major route changes. Six minor route changes, including five numerical abnormalities (-7, -17, +17, +21, and -Y) but also one structural aberration, t(3;21) (q26;q22), have been identified. At least one of these changes is found in 15% of all Ph-positive CML cases. Altogether, the four major route aberrations and the six minor route changes are present as part of the clonal evolution in 86% of CML with cytogenetic abnormalities in addition to the Ph chromosome.

Blast Crisis↗