Biomedical subjects

M Muleris

Publications and source records attributed to M Muleris.

At least 73 records · Page 4Linked to original sources

PubMed1987

Recurrent deletions of chromosomes 11q and 3p in anal canal carcinoma.

A cytogenetic study of 8 cases of anal canal cancer, including 1 cloacogenic and 7 squamous-cell carcinomas, was performed. All tumors exhibited chromosomal abnormalities. A rearrangement involving the long arm of chromosome 11 was seen in all instances, and, with the exception of the i (11q) found in one tumor, all the observed rearrangements resulted in a deletion of the distal segment. Rearrangements of chromosome 3, detected in 6 tumors, led to a deletion of the short arm in 5 cases. The association of these 2 deletions may characterize the anal canal carcinoma, the smallest common deleted segments being distal to 11q22 or q23 and 3p22.

Adult↗

PubMed1987

Noninvolvement of a constitutional heritable fragile site at 10q24.2 in rearranged chromosomes from rectal carcinoma cells.

A fragile site in chromosome band 10q24.2 was found in the lymphocytes of a patient ascertained for rectal carcinoma. The karyotype of 110 R-banded tumor cells was performed, showing two stemline formulas: 46,XXY,-1,-18,+20,der(6),t(1;6)(q21.1;q22.3),i(17q) and 46,XY,-1,-18,+8,+20,der(6),t(1;6),del(2)(p1600p22),i(17q). These findings are in agreement with our previous studies, which reported that the rearrangement of chromosome #17 and the loss of chromosome #18 are recurrent anomalies in colorectal carcinomas. In addition to these rearrangements, other anomalies were occasionally observed in tumor cells, but no breakages nor rearrangements involving band 10q24.2. The relationships between fragile sites and cancer breakpoints are discussed.

Chromosome Banding↗

PubMed1987

Characteristic chromosomal imbalances in 18 near-diploid colorectal tumors.

The cytogenetic study of 18 near-diploid colorectal tumors shows that the observed numerical and structural abnormalities resulted in recurrent chromosomal losses and gains. By order of decreasing frequencies, they are: monosomy 17p (16/18), partial or more frequently complete monosomy 18 (14/18), trisomy 20q (11/18), trisomy or tetrasomy 13 (10/18), monosomy lp and trisomies X and 8q (9/18). The absence of recurrent breakpoints in euchromatin contrasts with the high preponderance of breakage at various places of heterochromatic region. Because these tumors are characterized by very recurrent chromosomal imbalances, it is assumed that the observed chromosomal changes may be related to a recessive genetic determinism and to gene dosage imbalances.

Adult↗

PubMed1987

[Ploidy in colorectal cancer].

For several authors, DNA tumoral cell content represents an important prognostic factor in colorectal cancer. Samples obtained from 65 human colorectal cancers operated on between 1983 and 1986 were studied. Of 52 cases studied by flow cytometry 60 p. 100 were aneuploid tumors. The proliferative index was calculated in slightly over 50 p. 100 of the cases by DNA histogram analysis. During the same period 30 tumoral karyotypes were established by cytogenetic analysis. In 17 cases a comparison was possible between flow cytometry and cytogenetic results. In all cases a significant correlation was seen between the DNA histogram modal value and the mean number of chromosomes counted by cytogenic analysis. In this study, there was no statistical correlation between flow cytometry results and Dukes classification. Because of the short follow-up in our series, no prognostic value may be attributed to the DNA index.

Adult↗

PubMed1986

Imbalance of sex chromosomes, with gain of early-replicating X, in human solid tumors.

An imbalance of sex chromosomes was observed in several cases of solid tumors: colorectal, anal canal and breast carcinomas. Replication studies, using BUdR incorporation, show that in males there is a tendency towards a gain of early-replicating X and a deficiency of Y chromosomes. In females, there is a tendency towards a gain of early-replicating X and a loss of late-replicating X chromosomes. Although almost no replication studies have been published in the literature, making it impossible to distinguish between late- and early-replicating Xs, it is likely that a similar situation exists for several solid tumors other than those we have studied. A possible consequence of this imbalance is briefly discussed.

Anus Neoplasms↗

PubMed1986

Chromosomal study demonstrating the clonal evolution and metastatic origin of a metachronous colorectal carcinoma.

Detailed cytogenetic studies were performed on 3 samples of a metachronous rectal carcinoma. Two samples were obtained from the primary tumor, and one from a secondary growth which arose 10 months after surgical removal of the primary. All 149 R-banded metaphases analysed were abnormal and most likely derived from the same modified karyotype: 45, XY, -1, -18, +20 der(6) t(1;6) (q21.100;q22.3), i(17q). These data are consistent with our previous findings that the loss of chromosome 18 and of the short arm of chromosome 17 may be the primary chromosomal changes associated with carcinoma of the large bowel. From all the karyotypes observed, a typical clonal evolution could be reconstructed, indicating that the second tumor was indeed metastatic from the first one, based on similar chromosome markers. An identical secondary chromosomal anomaly, i.e. gain of chromosome 8 or X, occurred independently twice in two different cell populations during the evolution of this tumor.

Carcinoma↗

PubMed1986

Induction of increased salvage pathways of nucleotide synthesis by dosage effect due to chromosome imbalances may be fundamental in carcinogenesis: the example of colorectal carcinoma.

The cytogenetic study of colorectal carcinomas is consistent with the following sequence in the tumor evolution: rearrangement of chromosome 17 with loss of 17p and often gain of 17q, loss of chromosome 18, frequent del(5q), frequent del(1p) correlated with the gain of an early replicating X. At least one gene directly involved in nucleotide synthesis, especially in the de novo pathways for thymidine is located on each of these chromosomes or chromosomes segments. A model established on the gene dosage effect, which likely results of these chromosome imbalances, may be proposed: (1) increase of thymidine kinase activity (chromosome 17q) and thus of the salvage pathway of thymidine synthesis (2) decrease of thymidine de novo pathways by decreased of thymidylate synthase (chromosome 18) and of dihydrofolate reductase (chromosome 5q) and thus accumulation of 2'-deoxyuridine-5'-P, which saves 2'-deoxycytidine 5'-P (3) decrease of cytidylate (or uridylate) kinase (chromosome 1p) and thus accumulation of 2-deoxycytidine-5-PP and of uridine-5-P (UMP) decreasing the metabolisation of orotidine-5'-P, precursor of 2-deoxycytidine-5-PP, which (4) saves -D-5-ribosyl-PP (PRPP) or even conversion of orotidine-5'-P in PRPP. The later is the immediate precursor of nucleotides in their major salvage pathways synthesis: PRPP + base----nucleotide + PPi. This reaction which would be much activated needs hypoxanthine phosphorybosyl transferase (HPRT). Its gene is carried by chromosome X which is here duplicated in its active early replicating form.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome Aberrations↗

PubMed1986

Radiation induced inversions in human somatic cells.

Peri- and paracentric inversions induced by various types of ionizing radiation (gamma and alpha-rays, neutron and neon beams) are analysed. Their frequencies significantly increase for radiation doses greater than or equal to .5 Gy. Their distribution does not seem to be at random. Pericentric are detected 3 to 4 times more frequently than paracentric inversions. Some identical inversions are recurrently induced. A proportion reproduces inversions detected in human cytogenetics laboratories and a larger proportion, chromosomes of other primate species. It seems that breakages, which numbers are roughly proportional to chromosome lengths, lead to reassociations with a limited number of combinations.

Alpha Particles↗

PubMed1986

Inversions in evolution of man and closely related species.

By the comparative study of the karyotypes of many Primates, 35 inversions (25 peri- and 10 paracentric) having accumulated during evolution of species related to man were reconstructed. Some of them originated human chromosomes from more ancestral chromosomes still present in other primate species. Their detection in man would indicate the occurrence of reverse mutations. Other inversions occurred in ancestral chromosomes identical to those of man, and originated chromosomes of other Primates species. Their detection in man would indicate the occurrence of a convergent mutation. It is shown that such reverse and convergent mutations do occur. They are too frequently observed than by mere chance among patients ascertained in human cytogenetic laboratories. Their excess is still larger among radiation induced inversions in human cells. This demonstrates the nonrandom occurrence of inversions. In addition, it is concluded that inversions which have accumulated during evolution are more representative of mutagenesis than those detected in human cytogenetic laboratories.

Animals↗

PubMed1985

Inversion (14)(q12qter) or (q11.2q32.3): the most frequently acquired rearrangement in lymphocytes.

In a large study of chromosome rearrangements occurring in human lymphocytes from normal subjects, inv (14)(q12qter) or (q11.2q32.3) is found to be the most frequent, affecting 0.15% of mitoses. The same inversion is observed in the lymphocytes of the chimpanzee, indicating the ancestry of this inversion. It is not induced by ionizing radiations, and its frequency may be increased in Fanconi anemia, but not in ataxia telangiectasia. It may represent one of the steps of the process of leukemogenesis.

Animals↗

PubMed1985

Diagrammatic representation for chromosomal mutagenesis studies. III. Radiation-induced rearrangements in Pan troglodytes (chimpanzee).

A qualitative study is presented of chromosomal rearrangements induced by gamma-irradiation at 2 Gy and 3 Gy in peripheral blood lymphocytes of the chimpanzee Pan troglodytes. From a sample of 460 cells, karyotyped after R-banding, 1047 rearrangements were detected. Each type of rearrangement is analyzed according to the diagrammatic method previously developed. The non-random nature of the induction of the rearrangements is clear. The chimpanzee seems highly sensitive to the induction of dicentrics. This may be related to the existence, in its karyotype, of sensitive juxta-telomeric heterochromatin, much more frequently affected in the case of formation of dicentrics than of other types of rearrangements. Thus, the evaluation of radiation sensitivity of a given species based only on the yield of dicentrics may not have a general value for chromosomal mutagenesis.

Animals↗

PubMed1985

[Cytogenetic study of Cercopithecus wolfi, Cercopithecus erythrotis and a hybrid Cercopithecus ascanius X Cercopithecus pogonias grayi].

The karyotypes of two species of Cercopithecus, C. wolfi and C. erythrotis, as well as that of a hybrid C. ascanius X C. pogonias grayi, are described and compared. The karyotype of C. erythrotis is similar to that of C. ascanius and C. cephus described previously. The karyotypes of C. wolfi and C. p. grayi differ by a single inversion. The karyotype of the hybrid shows that the two parental species differ by five rearrangements, three fissions and two inversions, an observation in agreement with our previous interpretation.

Animals↗

PubMed1985

[Exact localization of several fragile sites remains uncertain. The example of fra(10) sensitive to folate].

The localization of the folate-sensitive fragile site first proposed to be at 10q24.2 was further assigned to 10q23. The study of one case using several banding techniques, and of 12 other unpublished cases studied with R-banding confirm the original localization, at the junction between 10q24.1 and 10q24.2. Because many reports propose that fragile sites induce further anomalies, we suggest that a re-study of the exact location of these sites with accurate methods is in order if misinterpretations are to be avoided.

Chromosome Banding↗

PubMed1985

Consistent deficiencies of chromosome 18 and of the short arm of chromosome 17 in eleven cases of human large bowel cancer: a possible recessive determinism.

Cytogenetic study of 11 cases of colorectal carcinoma was performed after R-banding. In all instances, there was a rearrangement involving chromosome 17 in its juxtacentromeric region, leading to the loss of its short arm. There was also a relative lack of chromosome 18, unrelated to a rearrangement of this chromosome in all but one case. Other anomalies, involving chromosomes 1 and 8 among others, were frequently but not systematically observed. The consistent lack of chromosome 18 and of the short arm of chromosome 17, leading to a complete or partial monosomy of these chromosomes in near diploid cells suggests that the passage to the hemizygous status of recessive genes carried by these chromosomes may play an important role in the development of colorectal carcinoma.

Adult↗

PubMed1985

[Rearrangement of the chromosome 17 in colonic adenocarcinoma].

Chromosome studies on five cases of large bowel adenocarcinoma show a systematic rearrangement of chromosome No. 17 after breakage in its juxtacentromeric region (band 17 q 11). A frequent involvement of chromosome No. 8 (juxtacentromeric break) and the loss of chromosome No. 18 are also noticed. A review of the literature strengthens the hypothesis of a preferential involvement of these chromosomes in large bowel cancer.

Adenocarcinoma↗

PubMed1984

Diagrammatic representation for chromosomal mutagenesis studies. I. Karyotypes most similar to that of man.

In an attempt to discover which primate species have the karyotypes most similar to that of man, the chromosome numbers, the Nombre Fondamental and the numbers of chromosomal rearrangements separating the karyotypes of many species were considered. In addition to man, 6 species were selected for their karyotypic similarities and 1 for its dissimilarity. A model representing the karyotypes, by 2 diagrams, is proposed for these 8 species. These diagrams characterize each karyotype, as well as the theoretical random distribution of break-points, after the effect of a clastogenic agent. This allows one to make quantitative analyses of any type of chromosomal rearrangement, with objective criteria, and should improve the study of chromosomal mutagenesis, and particularly interspecies comparisons.

Animals↗

PubMed1984

Diagrammatic representation for chromosomal mutagenesis studies. II. Radiation-induced rearrangements in Macaca fascicularis.

A qualitative study is presented of chromosomal rearrangements induced in peripheral blood lymphocytes of Macaca fascicularis, after exposure to gamma-irradiation at 2 Gy and 3 Gy. The use of a new diagrammatic representation allowed us to compare, for each type of rearrangement, the distribution of the observed break-points with the theoretical random distribution. It was concluded that chromosomal mutagenesis does not occur at random: an excess of involvement of small chromosomes is found for dicentrics and reciprocal translocations; an excess of telomeric breaks exists in dicentrics and paracentric inversions. In our sample of 27 pericentric inversions, the larger chromosomes are too frequently involved, 2 different inversions are observed at least twice and 7 (or 8) reproduce chromosomes of other primates.

Animals↗

PubMed1984

Chromosome study of Presbytis cristatus: presence of a complex Y-autosome rearrangement in the male.

The karyotypes of a female and of a male Presbytis cristatus are analysed. In the latter, there is a complex Y-autosome rearrangement. The phyletic position of this species, in relation to genus Colobus, previously studied, is proposed, considering the sequence of chromosomal rearrangements which occurred during their evolution. These rearrangements, in addition to the t(Y-autosome), are characterized by a high frequency of inversions, and above all, by several non-Robertsonian translocations which occurred very rarely during evolution of other Primates.

Animals↗