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F Mitelman

Publications and source records attributed to F Mitelman.

At least 19 recordsLinked to original sources
PubMed1992

Pseudodiploid karyotypes in adenosquamous carcinomas of the lung.

Pseudodiploid karyotypes with clonal structural rearrangements were observed in short-term cultures from two adenosquamous carcinomas (ASC) of the lung, a tumor type hitherto virtually uncharacterized cytogenetically. The karyotypes were 46,XX,der(1)t(1;14)(q44;q22),add(9)(q34) in the first tumor and 46,XX,i(17)(q10) in the second tumor. We suggest that ASC of the lung differ from other lung cancers by having pseudodiploid instead of massively aneuploid tumor stemlines.

Aneuploidy↗
PubMed1992

Trisomy 7 in nonneoplastic focal steatosis of the liver.

Cytogenetic analysis of short-term cultures of a nonneoplastic focal steatosis of the liver showed trisomy 7 as the sole chromosomal change. This finding, especially when viewed in light of previous reports describing +7 in nonneoplastic tissues, strongly suggests that trisomy 7 cannot be considered a tumor-specific abnormality when it occurs as the only change. The cell type in which +7 is present is not yet known.

Adult↗
PubMed1992

Cytogenetic analysis in the diagnosis of acute leukemia.

Acute leukemias are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the leukemia and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. The pattern differs between acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) and from subtype to subtype. Some abnormalities are so characteristic as to be virtually pathognomonic for particular types of leukemia. The importance of cytogenetic characterization of leukemias is thus two-fold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality in hematopoietic cells identifies the presence of a neoplastic disease. The aberration profile may reveal whether the patient has ALL or ANLL and which subtype it is. Remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern is an independent prognostic parameter that should be considered when the choice of therapy is made.

Chromosome Aberrations↗
PubMed1992

Nonrandom chromosomal rearrangements in pancreatic carcinomas.

Short-term cultures were initiated from 20 carcinomas of the pancreas, 17 of which could be successfully cytogenetically analyzed. In eight carcinomas, only normal karyotypes were detected, probably representing dividing stromal cells. Three cases had -Y as the sole anomaly, which also may have occurred in cells that do not belong to the tumor parenchyma. Massively rearranged karyotypes with modal chromosome numbers in the triploid (five cases) and diploid-triploid (one case) ranges were found in the remaining six carcinomas. Structural rearrangements, including deletions and unbalanced translocations, of the long arm of chromosome 6, involving bands q13 and q15 twice and q11 and q16 once, occurred in four tumors. All of these aberrations led to loss of chromosome material from 6q, always involving 6q15. Deletions and unbalanced translocations of the short arm of chromosome 1 also were found in four cases, affecting band p32 in three of them. In all four cases, the abnormalities resulted in loss of genetic material distal to 1p32. Chromosome 17 was involved in structural aberrations in three cases, twice as unbalanced translocations leading to loss of 17p material. Deletions of the short arms of chromosomes 3 and 8 were detected in two carcinomas. The most consistent numerical abnormalities were +2, +10, +11, +14, and tetrasomy 20, which were seen in all six cases. The findings suggest that structural rearrangements, or loss, of genes located on 1p, 3p, 6q, 8p, and 17p are of pathogenetic importance in pancreatic carcinogenesis.

Aged↗
PubMed1992

Cytogenetic analysis of 57 primary prostatic adenocarcinomas.

Cytogenetic analysis after short-term culture in vitro of primary tumor samples was attempted in 82 patients with prostatic cancer. Tumor material was obtained by radical prostatectomy or transurethral resection. Successful cytogenetic studies were performed on 57 tumors of which five were well, 30 moderately, and 22 poorly differentiated adenocarcinomas. Only normal karyotypes were found in 24 tumors. Structural nonclonal aberrations were detected in 18 and clonal karyotypic abnormalities in 15 tumors. The most common clonal numerical aberration was loss of the Y chromosome; a missing Y was found in six tumors, in three of these as the sole anomaly. Clonal structural chromosomal rearrangements, usually accompanied by numerical changes, were detected in 12 tumors. The rearrangements involved 18 of the 22 autosomes and the X chromosome. Chromosomes 1, 7, and 10 were most frequently affected. Deletions, duplications, inversions, insertions, and balanced as well as unbalanced translocations were represented. The breakpoints in chromosome 1 were scattered along both the short and long arms with no obvious clustering, whereas those in chromosomes 7 and 10 were clustered at bands 7q22 (two deletions and two duplications in four different tumors) and 10q24 (two translocations, one deletion, and one inversion in four tumors). One additional tumor displayed a derivative chromosome 10 with a breakpoint in 10q23, and one had monosomy 10. Altogether, these abnormalities resulted in loss of 10q24----qter in five tumors. Monosomy 8 and rearrangements of the short arm of chromosome 8 leading to loss of 8p21----pter were seen in four tumors. Double minute chromosomes were found in two tumors.

Adenocarcinoma↗
PubMed1992

Trisomy 2 as the sole chromosomal abnormality in a hepatoblastoma.

Short-term cultures of a fine-needle aspirate from a hepatoblastoma were analyzed cytogenetically. Trisomy 2 was found as the sole abnormality, yielding the karyotype 47,XY, + 2/46,XY. Because trisomy for all or part of chromosome 2 has been described, although together with other aberrations, in seven of the 11 hepatoblastomas hitherto reported, the finding of + 2 as the only anomaly in the present case strongly indicates that additional chromosome 2 material is of pathogenetic significance in this tumor type.

Carcinoma, Hepatocellular↗
PubMed1992

Clonal structural chromosome aberrations in nonneoplastic cells of the skin and upper aerodigestive tract.

Cytogenetic analyses of tumors of the skin and upper aerodigestive tract have repeatedly revealed small, pseudodiploid clones characterized by balanced structural rearrangements and a high frequency of cells with nonclonal structural aberrations. However, the lack of common cytogenetic denominators within the different histologic subtypes, the discrepancy between cytogenetic findings and data obtained from flow cytometric DNA content studies, and the occasional identification of tumors with massively rearranged karyotypes indicate that the chromosome rearrangements present in pseudodiploid cells have little to do with the tumorigenesis or progression. Further support for this conclusion, and indirect evidence that the pseudolipid clones probably do not represent the tumor cell populations, derives from the present study in which clonal and nonclonal structural rearrangements were also found in short-term cultures from nonneoplastic skin and pharyngeal mucosa. It is possible that the aberrations are present in subepithelial fibroblast that have accumulated DNA damage due to extensive exposure to potentially carcinogenic agents.

Adult↗
PubMed1992

Improved technique for short-term culture and cytogenetic analysis of human breast cancer.

Various growth media and procedures for tissue disaggregation and culturing were tested with regard to cell attachment, the type of cells to grow out, and the emergence of cytogenetically abnormal clones in cultures of 20 primary breast carcinomas. Clonal chromosome abnormalities were detected in 16 cases (80%). Our findings allow us to suggest a series of modifications of existing culturing and chromosome preparation techniques for breast cancer cytogenetic analysis. The improvements include: (1) combined mechanical and enzymatic disaggregation of the tumor samples, (2) initiation of short-term cultures in plastic flasks that have a Primaria-modified tissue culture surface or have been coated with Vitrogen 100, (3) use of serum-free growth medium, CDM-5, but with temporary (24 hours) enrichment with 20% FBS if rapid cell attachment is not achieved, (4) partial and sequential harvesting of the cultures, and (5) use of minimal volumes of hypotonic and fixative solutions during harvesting.

Aneuploidy↗
PubMed1992

Quantitative acute leukemia cytogenetics.

Using literature data on cytogenetic abnormalities in 3,612 cases of acute myeloid leukemia (AML) and 1,551-cases of acute lymphocytic leukemia (ALL), we have attempted to quantify the information value of finding the typical ALL- and AML-associated chromosome aberrations. Sensitivity, specificity, and predictive value of finding or not finding a given aberration were calculated for several diagnostic scenarios: for the differential diagnosis between ALL and AML when the patient is known to have acute leukemia, for the differential diagnosis among AML FAB subtypes in a patient with known AML, and for the differential diagnosis between ALL FAB subtypes in a patient with known ALL. The specificities were generally high, close to 1. The highest sensitivities in AML were found for +8, t(15;17)(q22;q11), t(8;21)(q22;q22), and -7 (all greater than 0.1), and in ALL for t(9;22)(q34;q11), t(4;11)(q21;q23), and +21 (again all greater than 0.1). In the AML subtypes, the highest sensitivities were 0.89 for t(15;17)(q22;q11) in M3, followed by 0.40 for t(8;21)(q22;q22) in M2, 0.30 for inv(16)(p13q22)/del(16)(q22)/t(16;16)(p13;q22) in M4, and 0.16 for t(9;11)(p21;q23) in M5. In the ALL subtypes, the highest sensitivities were 0.71 and 0.11 for t(8;14)(q24;q32) and t(8;22)(q24;q11), respectively, in L3, 0.23 for t(9;22)(q34;q11) in L2, and 0.18 and 0.13 for +21 and t(4;11)(q21;q23), respectively, in L1. The highest (1.0) positive predictive values in the AML versus ALL comparison were found for t(1;3)(p36;q21), inv(3)(q21q26), t(6;9)(p23;q34), t(7;11)(p15;p15), t(8;16)(p11;p13), t(8;21)(q22;q22), t(15;17)(q22;q11), and, as sole anomalies, for +4, +9, and +11. In the reverse comparison, ALL versus AML, positive predictive values of 1.0 were found for t(1;14)(p32-34;q11), dup(I)(q12-21q31-32), t(2;8)(p12;q24), t(8;14)(q24;q32), t/dic(9;12)(p11-12;p11-13), t(10;14)(q24;q11), and t(11;14)(p13;q11). Among the AML subgroups, the highest predictive values were: 1.0 for M3 if t(15;17), 0.91 for M2 if t(8;21), 0.86 for M4 if inv/del(16)/t(16;16), and 0.82 for M5 if t(9;11). Among the ALL subtypes, positive predictive values of greater than 0.8 were reached only for the L3-associated aberrations t(2;8) (1.0), t(8;14) (0.95), t(8;22) (0.87), and dup(I) (0.80). The highest negative predictive values were in AML 0.98 that the disease is not M3 if t(15;17) is not found, and in ALL 0.96 that the patient does not have L3 if a t(8;14) is not detected.

Chromosome Aberrations↗
PubMed1992

Whole-arm t(1;16) and i(1q) as sole anomalies identify gain of 1q as a primary chromosomal abnormality in breast cancer.

Cytogenetic analysis of four ductal breast carcinomas revealed net gain of 1q in all tumors. In the first tumor, the only change was that one chromosome 16 was replaced by a derivative chromosome consisting of 16p and 1q. The same unbalanced whole-arm translocation was also found in the second tumor, as the only aberration in one of four abnormal clones. In the last two cases, which also were characterized by cytogenetically unrelated clones, an extra i(1q) was present in one clone in both tumors as the sole aberration. Our findings suggest that gain of 1q is a primary chromosomal abnormality in breast carcinomas, in the sense that it is an early event that precedes the acquisition of more complex changes.

Adenocarcinoma, Mucinous↗
PubMed1992

Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).

Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12;16)(q13;p11). It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question. Using a cDNA probe that spans the CHOP coding region, we detected one rearranged and one wild type allele in nine of nine MLS with t(12;16). Using PCR generated, site-specific probes corresponding to the non-coding exons 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp PstI fragments that contain the first two exons and introns of the gene and the upstream promoter region. In contrast to the findings in MLS, no tumor without a t(12;16) exhibited aberrant CHOP restriction digest patterns. These tumors included one highly differentiated liposarcoma with abnormal karyotype but no involvement of 12q13, seven lipomas with various cytogenetic aberrations of 12q13-15, two uterine leiomyomas with t(12;14) (q14-15;q23-24), and one hemangiopericytoma and one chondroma, both of which also had 12q13 changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Near-haploid clones in a malignant fibrous histiocytoma.

Near-haploid solid tumors are very rare. In a storiform-pleomorphic malignant fibrous histiocytoma (MFH) of bone, we found three cell populations: one with a near-haploid, a second with a near-diploid, and a third with a near-tetraploid chromosome number. The near-haploid cells had few structural rearrangements: i(12p) and t(13q21q) in one clone, and these two and an additional t(19;?)(p11;?) in another clone. One structurally normal copy of all chromosomes was also present, except that the only chromosome 13 was involved in the t(13q21q). There were also two near-diploid clones, one without the t(19;?) and one with a single copy of this derivative chromosome. This is the first tumor with i(12p) among bone and soft tissue tumors.

Chromosome Inversion↗
PubMed1992

Supernumerary ring chromosomes in five bone and soft tissue tumors of low or borderline malignancy.

Five tumors (two myxoid malignant fibrous histiocytoma, two dermatofibrosarcoma protuberans, and one parosteal osteosarcoma) with ring chromosomes as the sole cytogenetic anomaly or as the only structural rearrangement were observed in a series of 60 karyotypically abnormal, nonlipogenic bone and soft tissue tumors (BST). All five tumors were of borderline or low malignancy. These findings support the suggestion that supernumerary ring chromosomes as the sole structural chromosomal aberration are not associated with any particular histopathologic diagnosis but may characterize a group of BST of borderline or low malignancy.

Adolescent↗
PubMed1992

Embryonal rhabdomyosarcoma with 100 chromosomes but no structural aberrations.

An embryonal rhabdomyosarcoma was analyzed cytogenetically after short-term culturing. The tumor was located in the scrotum of an 18-year-old man who, at the age of 4, had been treated for a rhabdomyosarcoma in the orbita. The chromosome number was 100. No structural aberrations were present. There were 2-7 copies of each chromosome type with particular excess of chromosomes 8, 12, and 22, and a relative deficit of chromosome 15.

Adolescent↗
PubMed1992

Recurrent chromosome aberrations in abdominal smooth muscle tumors.

Short-term cultures of four abdominal smooth muscle tumors, three leiomyosarcomas and one leiomyoma, were analyzed cytogenetically. A low-grade malignant, epithelioid leiomyosarcoma had a normal karyotype. The other two leiomyosarcomas had abnormal karyotypes; one was near-diploid, and the other was near-triploid. Structural rearrangements of the short arm of chromosome 16 and monosomies of chromosomes 14, 15, and 22 were observed in both tumors. When our cases and previously published abdominal leiomyosarcomas are viewed in conjunction, loss of chromosomes 14, 15, and 22 are the most frequent abnormalities. The leiomyoma, the second cytogenetically abnormal nonuterine leiomyoma reported to date, had a hyperdiploid karyotype with a chromosome number of 56 and structural rearrangements of chromosomes 9, 14, and 19. The only aberrations similar to those observed in the previously reported esophageal leiomyoma were trisomies of chromosomes 7 and 8.

Abdominal Neoplasms↗
PubMed1992

Cytogenetic findings in three primary hepatocellular carcinomas.

Short-term cultures of three primary hepatocellular carcinomas were cytogenetically analyzed. Case 1 displayed a normal karyotype. Case 2 had, in addition to cells with a normal male chromosome complement, a clone with -Y. In case 3, two abnormal clones were found, one with -Y and one with a highly aberrant karyotype: [formula: see text] Our results, collated with the findings in one previously published primary hepatocellular carcinoma and in three cell lines, suggest that structural changes of chromosomes 1 and 6, leading to loss of 1p and 6q material, and loss of chromosome 16 are frequent events in hepatocellular carcinogenesis.

Aged↗