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M Muleris

Publications and source records attributed to M Muleris.

At least 37 records · Page 2Linked to original sources
PubMed1995

Chromosome mapping of 11 human probes in the region 5q2-->q3 by fluorescence in situ hybridization.

Using single- and double-color fluorescence in situ hybridization (FISH), 11 probes from the human chromosome region 5q2-->q3 are mapped. The following map order is proposed, from proximal to distal: 5q21.3-->q22: 15A6 (D5S136), YN5.64, CRI-L372 (D5S49), YN5.48 (D5S81): 5q22: EF5.44 (D5S135), APC; 5q22-->q23.1; CI5.23, L5.69 (D5S137), CRI-T39 (D5S64), MC5.61 (D5S84); 5q31.1-->q31.2: CRI-L1265 (D5S52).

Chromosome Mapping↗
PubMed1995

[Two colons--two cancers? Proximal or distal adenocarcinoma: arguments for a different carcinogenesis].

The purpose of this review is to study the literature concerning normal colon and colorectal cancer for evidencing that the location of the primary proximal or distal tumor may determine two categories of carcinogenesis. The proximal or distal normal colon can be considered as two different organs. Their embryologic origins are different, the splenic flexure starts the distal segment. Antigenic pattern as well as the use of metabolic pathways, such as that of glucose, butyrate and polyamines differ. Epidemiologic, macroscopic and histological features and the inherited and acquired genetic abnormalities allow in some cases to distinguish between two types of cancer according to their proximal or distal location. These two forms are not entirely different and these features can overlap. However the recognition of these two different forms of colon cancer, must be taken in account for clinical or basic research and evaluation of data.

Adenocarcinoma↗
PubMed1994

[Genetic anomalies of colorectal cancers. Their role in guiding therapeutic indications].

Progress in detecting genetic anomalies with proven prognostic value in colorectal cancers offers a means of selecting adjuvant therapy with the best probability of success. Several methods are currently used. With flow cytometry, a significant correlation between primary tumour ploidy and hepatic metastasis has been demonstrated. Caryotypes of tumour cells provides a means of exposing segmental or total chromosome loss and subsequent classification leads to a better understanding of tumour heterogeneity. New techniques in molecular biology are used to describe mutations. Monoclonal antibodies can then be developed against the epitopes involved. Based on these different methods clinicians and fundamentalists can analyse treatment results with more precision and thus adopt the most effective treatment protocol.

Chromosome Aberrations↗
PubMed1994

Gene dosage and expression, and enzyme activity of thymidine kinase and thymidylate synthase in xenografted colorectal adenocarcinomas.

Cytogenetic studies performed on human colorectal tumors have revealed 2 specific patterns of chromosomal anomalies. The major pattern, known as the monosomic type (MT), is characterized by the loss or deletion of chromosomes 18, 17 (short arm 17p) and, less frequently, 1p, 4, 15, 5 (long arm 5q) and 21. The other one, known as the trisomic type (TT), is characterized by the gain of several chromosomes: 7, 12, X, 5 and 8. Losses of chromosome 18 and of the 17p arm never coexist in TT tumors. It was observed that many chromosome losses or deletions involved genes encoding for enzymes of the de novo pathways of nucleotide synthesis. In contrast, gains involved genes encoding for enzymes of the salvage pathways of the same metabolism. This led to the hypothesis that chromosome imbalances corresponded to those of nucleotide synthesis in tumor cells. Such an interrelation was confirmed by the dosage of thymidylate synthase (TS) and thymidine kinase (TK) activities in a series of colorectal grafted tumors. This study has been expanded to a larger series of xenografted tumors (23 cases) in which both TS and TK activities were studied, in parallel with an analysis of mRNA, by Northern blotting. The amount of mRNA was found to correlate with the number of gene copies calculated from cytogenetic data, indicating a direct gene-dosage effect. It also correlated with enzyme activities, but less strongly. This suggests the existence of an efficient post-transcriptional regulation, in particular for TS, whose level of expression varies over a wide range. Such variations may explain the diversity of responses to chemotherapy.

Adenocarcinoma↗
PubMed1994

A rapid and simple method to isolate and characterize highly polymorphic markers from the centromeric regions of the human chromosomes.

Using oligonucleotide primers complementary to the 3' ends of either the Alu or the L1Hs consensus sequences in conjunction with a primer complementary to alpha satellite subsets specific to different human chromosomes, it was possible to detect and characterize polymorphisms originating from the microsatellites which are often present downstream these repetitive elements. The methodology does not require cloning, sequencing or synthesis of specific primers. Centromeric location was confirmed by linkage analysis, in situ hybridization and sequencing. The method is proposed for the generation of polymorphic markers from all centromeric regions.

Base Sequence↗
PubMed1994

Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique.

A modified comparative genomic hybridization (mCGH) technique was applied to a series of 17 primary breast carcinomas in which cytogenetic study (CG) demonstrated the presence of homogeneously staining region(s), suggesting the occurrence of DNA amplification. mCGH demonstrated recurrent amplifications of the whole chromosome arms 8q (9 times) and 1q (7 times) and of DNA loci in the following bands: 11q13 (6 times), 9p13 and 17q21.1 (4 times), 1q21.1 and 16p11.2 (3 times), and 8q22, 8q24.1, 10q22, 15q26, 17q23, and 20q13.3 (twice). Amplification of whole chromosome arms is likely to have resulted from unbalanced translocations or isochromosomes, whereas amplifications of smaller chromosomal segments probably arose through real DNA amplification processes. In all tumors but one, more than one amplified locus was detected. The fact that many chromosomal sites were involved suggests that the process of amplification is complex and that many genes are potential targets.

Breast Neoplasms↗
PubMed1994

Cytogenetic study of 30 colorectal adenomas.

The cytogenetic analysis of 30 colorectal adenomas obtained from 24 patients is reported. Only normal karyotypes were observed in eight cases. Among the 22 adenomas with abnormal karyotypes, 15 showed clonal anomalies. Chromosome gains involving chromosomes 13, 20, 7, 9, and 12 were recurrently observed. Chromosome 18 was frequently lost or involved in translocations at bands q21-q22. More chromosome alterations were observed in the cases in which histologic examination revealed severe dysplasia or a carcinomatous component. These anomalies are discussed in relation to those described in colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1994

Detection of methylcytosine-rich heterochromatin on banded chromosomes. Application to cells with various status of DNA methylation.

A procedure including incorporation of 5-bromodeoxyuridine (BrdU) in DNA and a thermal denaturation step was developed to obtain both R-banding and efficient binding of anti-5-methylcytosine antibodies on metaphase chromosomes. BrdU incorporation improved the efficiency of antibody binding disclosed by immunofluorescence staining. This method allowed semiquantitative analysis of the antibody binding sites on straightforward characterized metaphase chromosomes and was applied to normal human lymphocytes and lymphoblastoid cell lines for which DNA methylation status had been previously analyzed. A correlation was established between level of DNA methylation and the semiquantitative estimate of antibody fixation. This procedure can be used to study DNA methylation on metaphase chromosomes in transformed and cancerous cell lines.

Chromosome Banding↗
PubMed1994

Chromosome instability in lymphocytes from patients affected by or genetically predisposed to colorectal cancer.

To determine whether there are chromosomal clues to inherited forms of colorectal cancer, we studied chromosome instability in lymphocytes cultured from persons with sporadic colorectal cancer before treatment and from persons with a genetic predisposition to colorectal cancer due to adenomatous polyposis coli, Peutz-Jeghers syndrome, or juvenile polyposis. Spontaneous aberrations of chromosome number and structure were scored and compared to control studies by the same methods. Sex chromosome aneuploidy was found increased in patients. Autosomal aneuploidy was not increased. Chromosome breakage was elevated in young persons genetically predisposed to colorectal cancer compared to young patients with sporadic colorectal cancer. Chromosome rearrangements, other than those of chromosomes 7 and/or 14, rose with age, particularly in patients. Despite considerable interindividual variations, it would seem that increased chromosome breakage and rearrangement in addition to sex chromosome aneuploidy may be signs of chromosome instability in the predisposition to colorectal cancer.

Adenomatous Polyposis Coli↗
PubMed1994

The frequency of micronuclei with X chromosome increases with age in human females.

The rate of micronuclei counted on lymphocyte cultures from five healthy female donors, 27-80 years old, increased with age. Using pXBR1 probe, specific for the alphoid DNA of the X chromosome, the presence of this chromosome was investigated by FISH (fluorescence in situ hybridization) in both micronuclei and metaphases. Both X aneuploidy and frequency of X chromosome per micronuclei increased with age. However, this overinvolvement of X chromosome was not sufficient to explain the overall increase of micronuclei with age, suggesting that autosomes are also involved. Thus, the higher increase of X than autosome aneuploidy in lymphocytes may result from both an excess of X chromosome losses and a better survival of cells with a monosomy X.

Adult↗
PubMed1994

Mapping of 18 probes on human chromosome 18 using single- and double-color FISH.

Fluorescence in situ hybridization (FISH) techniques were applied to the mapping of 18 probes from chromosome 18, permitting seven new assignments: D18S16 (18p11.31), D18S12 (18p11.1), D18S1 (18q12.2), D18S13 (18q21.31), D18S18 (18q21.31), D18S14 (18q21.33), and D18S17 (18q23). In addition, the localization of D18S3 in 18p11.3 was confirmed and that of D18S6, previously mapped in 18p11, was changed to 18q21.13. Finally, a more accurate mapping for nine probes was proposed: D18S7 (18q12.2), D18S10 (18q12.2), D18S24 (18q21.13), D18S8 (18q21.13), GRP (18q21.31), BCL2 (18q21.33), D18S5 (18q22.1), D18S19 (18q22.1), and D18S11 (18q22.3). The ordering of probes located in close proximity was made possible by combined use of single-color FISH with direct assignment on banded chromosomes, chromosomal length measurements, and double-color FISH.

Chromosome Mapping↗
PubMed1994

Increased FISH efficiency using APC probes generated by direct incorporation of labeled nucleotides by PCR.

Probes of various sizes from the adenomatous polyposis coli gene (APC) were directly biotinylated by polymerase chain reaction (PCR) from genomic DNA. PCR labeling gave high efficiency in detection of fluorescence in situ hybridization (FISH) signals. Probes as small as 250 base pairs could be visualized through a fluorescence microscope without any image processing.

Adenomatous Polyposis Coli↗
PubMed1994

In situ hybridization approach at infragenic level on metaphase chromosomes.

Analysis of the retinoblastoma locus (RB1) by in situ hybridization at the infragenic level was done using human chromosomes. A high level of resolution was attained with nonisotopic in situ hybridization on banded chromosomes in both fluorescence and electron microscopy. DNA sequences less than 100 kb apart could be positioned on band 13q14 in the order expected from molecular mapping. These observations suggest that the DNA target of hybridized probes on metaphase chromosomes may correspond to nucleoprotein loops giving a resolution comparable to that obtained in interphase nuclei.

Genes, Retinoblastoma↗
PubMed1994

[Genetic anomalies of colorectal cancers].

The prognosis of colorectal cancer has been based essentially on pathological data for many years. The analysis of genetic anomalies has led to fundamental progress and clinical advances. Genetic anomalies are routinely studied. 1--Flowcytometry evaluates the quantity of DNA in the nucleus during the cell cycle. 2--Cytogentics is the study of karyotype anomalies by loss or gain of chromosome material and structural changes. 3--Molecular biology gives a means of recognizing chromosome losses and especially to study oncogenic or antioncogenic mutations. These analyses allow: 1--an evaluation of their value as a prognosis factor and thus their use for indicating adjuvant medical and/or surgical treatments. 2--an understanding of cancerogenic processes. 3--the development of future therapeutic techniques based on a better understanding of the mechanisms involved. 4--familial counselling in high risk families and an examination of responsible or favouring genes in certain familial cancers. Research into familial forms has recently led led to the demonstration of genetic alterations located on chromosomes 1 and 2. These anomalies called RER correspond to alterations found on tumors. Studying these alterations will allow better prediction of high risk subjects in cancer families without polyposis.

Colorectal Neoplasms↗
PubMed1994

Oncogene amplification in human gliomas: a molecular cytogenetic analysis.

Nine cases of malignant gliomas were selected for the presence of double minutes (dmin) or homogeneously staining regions (hsr) detected by conventional cytogenetics. Analyses were performed on fresh (2 cases) or xenografted (5 cases) tumors or both (2 cases). A modified comparative genomic hybridization technique (mCGH) was applied exhibiting a single amplified locus in 8 tumors and 4 amplified loci in one tumor. Recurrent sites of amplification were detected in 7p11-p12 (5 cases) and 1q32.1 (2 cases). Signals were also observed in 4q11-q12, 5p15.1, 7q31, 8q24.1 and 9p2 in one tumor each. Southern blotting demonstrated that the genes for EGFR (epidermal growth factor receptor), PDGFRA (platelet derived growth factor receptor alpha), MET and MYC oncogenes were involved in 7p11-p12, 4q11-q12, 7q31 and 8q24.1 amplifications, respectively. These amplifications were found by in situ hybridization on tumor spreads, in dmin or episomes for EGFR, dmin for PDGFRA and MET, and hsr and dmin for MYC genes. Other mCGH signals, for which no target genes could be proposed, were confirmed by chromosome paintings on tumor metaphases. In one of the tumors, the coamplification of DNA from 5p15.1 and 9p2 bands in the same dmin was demonstrated.

Adult↗
PubMed1993

Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients.

In humans, alteration of the tumor suppressor gene, APC, causes adenomatous polyposis coli, a condition causing predisposition to colorectal cancer. The syndrome inconsistently associates characteristic patches of congenital hypertrophy of the retinal pigment epithelium (CHRPE). Ocular examination revealed that patients expressing CHRPE tend to cluster within specific families. The exact APC mutation was identified in 42 unrelated patients. In all cases these mutations were predicted to lead to the synthesis of a truncated protein. The extent of CHRPE was found to be dependent on the position of the mutation along the coding sequence. CHRPE lesions are almost always absent if the mutation occurs before exon 9, but are systematically present if it occurs after this exon. Thus, the range of phenotypic expression observed among affected patients may result in part from different allelic manifestations of APC mutations.

Adenomatous Polyposis Coli↗
PubMed1993

Chromosome 12 alterations and c-Ki-ras mutations in colorectal tumors.

c-Ki-ras mutations and gains of chromosome 12, where this gene is mapped, were both studied in a series of 47 colorectal cancers. Mutations at codon 12 and 13 were detected in 17 (36%) and gains of chromosome 12 in 7 (15%) cases. In this sample, gains of chromosome 12 occur in tumors either with or without c-Ki-ras mutations, suggesting that gains of chromosome 12 are independent from the mutation of c-Ki-ras.

Chromosomes, Human, Pair 12↗