Progress in solid tumor cytogenetics.
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Biomedical subjects
Publications and source records attributed to C Turc-Carel.
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A translocation that involves chromosome X (band p11.2) and chromosome 18 (band q11.2) was observed in short-term in vitro cultures of cells from five synovial sarcomas and one malignant fibrous histiocytoma. In four of these tumors, the translocation t(X;18)(p11.2;q11.2) was reciprocal. The two other tumors had complex translocations: t(X;18;21)(p11.2;q11.2;p13) and t(X;15;18)(p11.2;q23;q11.2). A translocation between chromosomes X and 18 was not detected in other histological types of soft tissue sarcoma. The X;18 rearrangement appears to characterize the synovial sarcoma and is the first description of a primary, nonrandom change in the sex chromosome of a human solid tumor.
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Detailed clinical histories and cytogenetic investigations using short-term cultures are reported in three typical benign lipomas. Although a diploid (normal) karyotype was observed in two cases, a reciprocal chromosome translocation t(3;12)(q28;q14) was found in the third case, which was briefly reported previously. These data are discussed in light of a lipoma with similar karyotypic changes reported by Heim et al. and a similar translocation observed by us in malignant myxoid liposarcomas. The nonrandom involvement of segment 12q13-q14 in benign and malignant lipomatous tumors suggest a common basis for at least one of the possible multiple steps in the genesis of neoplastic processes.
Detailed chromosome studies, briefly reported previously, from short-term cultures of tumor cells from myxoid liposarcomas are reported. A common reciprocal translocation, t(12;16)(q13;p11), was found in three cases and a complex t(1;12;16)(p11;q13;p11) in the fourth one. This nonrandom primary change, not described before in solid tumors, could characterize the myxoid form of liposarcoma. The involvement of a closely located breakpoint on chromosome #12 in a reciprocal t(3;12)(q28;q14) described in a lipoma in the previous article of this series, suggests a common basis in the biological process of proliferation of tumors sharing a common histogenesis.
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In two patients with chronic myeloid leukemia (CML), the nature of the chromosomal rearrangement giving rise to "masked" Ph has been studied by in situ hybridization of human c-abl sequences. The c-abl probes hybridized to the 22q11 region of the "masked" Ph, demonstrating that translocation of sequences from 9q34 to the Ph did occur exactly as in standard Ph or in other types of variants previously studied. These results provide additional evidence for the occurrence of a constant molecular rearrangement in Ph-positive CML.
Somatic cell hybrids, obtained after fusion of translocation (11;22)-positive Ewing sarcoma cells and Chinese hamster fibroblasts, were assayed for the presence of immunoglobulin C lambda, Philadelphia chromosome breakpoint cluster region, and c-sis oncogene sequences. It was found that c-sis was translocated from chromosome 22 to chromosome 11 in the Ewing sarcoma cells used, indicating that the breakpoint must be proximal to this locus. Moreover, we found that the chromosome 22-linked C lambda and breakpoint cluster region sequences are not translocated. This result confirms an earlier cytogenetic observation that the Ewing sarcoma-associated breakpoint in chromosome 22 is distal to those observed in translocation (8;22)-positive Burkitt lymphoma and in Philadelphia chromosome-positive chronic myeloid leukemia.
Ultrasonic examination in a thirty five years old woman about to undergo midtrimester amniocentesis suggested an intra abdominal fetal mass. The mass was a grossly distended urinary bladder. The pregnancy was terminated at 20 weeks. Necropsy was confirmative for a prune-belly syndrome. Chromosomal analysis demonstrated a 47 XY + 18 karyotype.
A detailed banded chromosome analysis was performed in five established Ewing's sarcoma (ES) cell lines originating from four unrelated patients in relapse. Of various numerical and structural abnormalities, a reciprocal translocation between chromosomes #11 and #22, t(11;22)(q24;q12), was observed in four of the lines. The t(11;22) was seen in every cell in three lines; in the fourth, it was seen in only 21% of the cells considered stemline, but the der(22) was present in the remaining 79% of cells. These results suggest that t(11;22)(q24;q12) is a chromosomal change specific to ES cells, in which the rearrangement of chromosome #22 could be the consistent karyotypic feature and the crucial step in terms of cell proliferation. Other, nonrandom chromosomal changes were found: monosomies 2p11----2pter, 10q25----10qter, and 17pter----17q11, and partial trisomies 1q21----1q31 and 8q24.1----8q24.2. The role of the therapeutic regimen received by these patients must be evaluated with regard to the formation of a wide variety of homogeneously staining regions, which were observed in every cell line, particularly on the short arm of chromosome #7, which was observed in three of the five cell lines.
A review on the association between acute leukemias (AL) and constitutional chromosome abnormalities (CCA) is presented. AL, myeloblastic or lymphoblastic according to age are 18 to 20 times more frequent in Down Syndrome (DS) children than in non DS children. The incidence of acquired chromosome abnormalities is similar in leukemic cells of DS and non DS patients but the type of anomalies, in the leukemic myeloblastic cells of DS, are different : hyperdiploidy, excess of C, F and G. Gain of chromosomes 8, 19 and 22 would characterize leukemic myeloblasts in an early stage of differentiation. Recent data on transient leukemoid reactions show that a 21 in DS appears to be predisposing factor in the development of AL. Association between AL and other balanced or unbalanced CCA appears until now to be fortuitous.
Chromosome banding techniques have been useful to define abnormal chromosomes in acute leukemia. The comparison between cases reported from different centers has been possible only with the acceptance of a universal system of classification and nomenclature for acute leukemia as well as for chromosomal rearrangements. Chromosomes abnormalities in acute leukemia are found in about 50 per cent of patients. They appear to be non random. Clinical, morphologic and cytogenetic findings have been correlated. Diagnosis and prognosis significance of chromosome abnormalities is of importance. The problem of normal or so called normal cells in 50 per cent of acute leukemia is set.
In vitro culture of hairy cells were successful in 5 patients with hairy cell leukemia: splenic cells were cultured in methyl cellulose plus PHA-leucocyte conditioned stimulation medium for 7 days. Plating efficiency was 0.5% with colony cells having morphological and cytochemical characteristics of hairy cells. A linear correlation between the number of cells plated and the number of colonies produced was found for cell concentrations varying from 5.10(4) to 5.10(5).
Chromosome studies were performed on 5 Ewing sarcoma cell lines. An identical reciprocal translocation t(11; 22) (q24; q12) was found in 4 cell lines established from 3 different tumors. These results, associated with those obtained at the same time and independently from fresh tumor cells, suggest that the translocation t(11; 22)(q24; q12) may be a chromosomal marker characteristic of Ewing sarcoma cells. This translocation involves the chromosome 22 on which the H-c-sis oncogene has been located; it could be used as a new tool for exploring the role of genetic transposition in the malignant cell transformation.
Two new cases of 69 XXY triploidy in live-born neonates are reported. As in 40 others cases of literature observed after 24 weeks of gestation, this chromosome abnormality was lethal. The clinical features are: a large posterior fontanelle, low set ears, syndactylies of hands and feet, and genital abnormalities in the presence of a 69 XXY karyotype. The first patient present a macrocytosis of red blood cells. Macrocytosis, large polymorphonuclear leukocytes and platelets can evoke the diagnosis of triploidy in a malformed newborn.