Alternate centromere inactivation in a pseudodicentric (15;20)(pter;pter) associated with a progressive neurological disorder.

A 13 year old male with a severe progressive neurological disorder was found to have a pseudodicentric chromosome resulting from a telomeric fusion 15p;20p. In lymphocytes, the centromeric constriction of the abnormal chromosome was always that of the chromosome 20, while in fibroblasts both centromeres were alternately constricted. Cd staining was positive only at the active centromere, but a weak anticentromere immunofluorescence was present at the inactive one. We suggest that centromere inactivation results from a modified conformation of the functional DNA sequences preventing normal binding to centromere specific proteins. We also postulate that the patient's disorder, reminiscent of a spongy glioneuronal dystrophy as seen in Alper's and Creutzfeldt-Jakob diseases, may be secondary to the presence of the pathogenic isoform of the prion protein encoded by a gene mapped to 20p12----pter.

Roberts-SC phocomelia syndrome with exencephaly.

We report a 18 weeks old fetus with the typical limb reduction anomalies of SC phocomelia syndrome, associated with exencephaly and unilateral anophthalmia, a feature previously reported in only 2 cases of severe Roberts syndrome. This observation brings another argument for lumping both diseases in a unique Roberts-SC phocomelia syndrome. Diagnosis was settled by the observation of premature centromeric splitting.

Prenatal diagnosis using deletion studies in Duchenne muscular dystrophy.

Accurate carrier testing and prenatal diagnosis in Duchenne muscular dystrophy (DMD) families is facilitated when an Xp21 deletion is found to be segregating within a family. We discuss the results of the DNA testing in two families, one in which DNA from affected males was available for study and the other in which no DNA from an affected male was available. Factors complicating the counselling of DMD deletion families are outlined.

High yield of micronuclei and micronuclei premature chromosome condensation in a mouse tumor cell line cultured in vivo with prearrested mitotic metaphases.

It is generally argued that micronuclei and micronuclei premature chromosome condensation (MN PCC) in stable cell lines occur only after treatment with potent clastogens, mutagens or carcinogens. In the present paper we report on the occurrence of micronuclei and MN PCC (predominantly of S type) at a high frequency in a mixed in vivo culture of prearrested mitotic metaphases with an asynchronous population of mouse ascites tumor cells (S180) without the aid of any clastogen, mutagen or carcinogen.

Characterization of human embryonal carcinoma cell lines derived from testicular germ-cell tumors.

Four human embryonal carcinoma (EC) cell lines (ITO, NEC 8, NEC 14, NEC 15) derived independently from testicular germ-cell tumors were established in vitro. In their xenografted tumor tissues, all of them exhibited histological characteristics consistent with EC. The cell-biological characterization of these human EC cell lines was investigated with reference to well-known murine EC cell lines. This included examination of their morphology, growth, tumorigenic potential, karyotype, cell-aggregate formation, HLA expression, large glycopeptides, AFP and HCG production, plasminogen-activator secretion, and LDH profiles. Three (ITO, NEC 14, NEC 15) of these human EC cell lines shared cell-biological characteristics consistent with typical EC, but one of them (NEC 8) differed from the others with respect to its rapid growth, high tumorigenic potential, formation of solid cell aggregates, and less differentiated, solid histological pattern. Thus, it is suggested that there are several developmentally different types of human EC cells. The relationship between the properties of these human EC cell lines and their differentiation potential is discussed.

Chromosome-breakage syndromes: different genes, different treatments, different cancers.

Comparison of the strikingly different distributions of types of cancer that occur in the genetic disorders that feature chromosome instability raises several interesting points. (a) Bloom's syndrome: the distribution suggests that many of the cancers that occur with regularity in the general population just occur more commonly and at an earlier age. (b) Ataxia telangiectasia: cancers of many types are increased in frequency, but lymphoreticular cancers are exceptionally common, the case also in several other genetically determined immunodeficiency disorders. Both Bloom's syndrome and ataxia telangiectasia share defective immunity as a major clinical feature, but the respective roles, if any, of it and of chromosome instability in producing the cancer predispositions are unknown. (c) Fanconi's anemia: cancer apparently has become common only recently. The types and distribution which occur are unusual. Fanconi's anemia cells have been shown to be hypertransformable by oncogenic virus and to be defective in handling certain types of DNA damage (as well as to manifest chromosome instability) so that the recent increase in cancer incidence is both surprising and unexplained. The degree of cancer proneness of Fanconi's anemia per se, untreated by modern methods, must at present be considered unknown. (d) Xeroderma pigmentosum: the cancer predisposition apparently extends only to cells which receive solar damage, i.e., to skin and eye. This would not have been predicted in view of the fact that the cellular mechanism is defective for repairing DNA damage produced not just by sunlight but also by certain classes of chemical carcinogens.

The clonal evolution of tumor cell populations.

It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.

[Cytogenetic study of the blood cells and lymph nodes in the process of the development of experimental lympholeukosis in calves]. / Tsitogeneticheskie issledovanie kletok krovi i limfouzlov v protsesse razvitiia éksperimental'nogo limfoleikoza u teliat

The karyotypes of peripheral blood lymphocytes were examined in 72 hour cultures in the process of the induced lymphatic leucaemia development in calves, as well as the karyotypes of one-layer transplantated tissue cultures of blood cells and lymph nodules of the same calves. The increase in hyperdiploid cell ratio in all investigated tissue cultures was detected.

[A cell-line with 27 chromosomes in a human acute leukemia (author's transl)]. / Clone cellulaire a 27 chromosomes dans une leucémie aiguë humaine

Chromosomal analysis of the bone-marrow aspirate of a five years old girl suffering acute leukemia revealed a cell-line carrying 27 chromosomes. Banding by controlled heating denaturation showed that, in these cells, all chromosomes are haploid, except chromosomes: X, 10, 18, 21. This cell-line, not seen during remission, was found during relapse, in addition to another one with 54 chromosomes. The caryotype of this last clone corresponded to the duplication of the chromosome set found in the first cell-line. The authors discuss two problems: the possible correlations between the clinical evolution and the biological data; the problem raised by the survival and proliferation of such an hypodiploid cell-line.

Epstein-Barr virus: transformation, cytopathic changes, and viral antigens in squirrel monkey and marmoset leukocytes.

Blood leukocytes of two species of new world primates, other than human, transform following exposure to Epstein-Barr virus. The transformed simian cells produce Epstein-Barr virus antigens and infectious (transforming) virus. The simian lymphoblastoid cells form multinucleate giant cells that appear to be selective sites for the production of Epstein-Barr virus. Multinucleate cells reveal intranuclear inclusions; in both species, a large proportion of giant cells contain Epstein-Barr virus antigen detectable by immunofluorescence.