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A Bernheim

Publications and source records attributed to A Bernheim.

At least 37 records · Page 2Linked to original sources
PubMed2001

Asymmetrical segregation of chromosomes with a normal metaphase/anaphase checkpoint in polyploid megakaryocytes.

During differentiation, megakaryocytes increase ploidy through a process called endomitosis, whose mechanisms remain unknown. As it corresponds to abortive mitosis at anaphase and is associated with a multipolar spindle, investigation of chromosome segregation may help to better understand this cell-cycle abnormality. To examine this variation, a new method was developed to combine primed in situ labeling to label centromeres of one chromosome category and immunostaining of tubulin. Human megakaryocytes were obtained from normal bone marrow culture. By confocal microscopy, this study demonstrates an asymmetrical distribution of chromosomes (1 or 7) either between the spindle poles at anaphase stage of endomitosis and between the different lobes of interphase megakaryocyte nuclei. The metaphase/anaphase checkpoint appears normal on the evidence that under nocodazole treatment megakaryocytes progressively accumulate in pseudo-metaphase, without spontaneous escape from this blockage. Immunostaining of p55CDC/hCDC20 with similar kinetochore localization and dynamics as during normal mitosis confirms this result. HCdh1 was also expressed in megakaryocytes, and its main target, cyclin B1, was normally degraded at anaphase, suggesting that the hCdh1-anaphase-promoting complex checkpoint was also functional. This study found the explanation for these unexpected results of an asymmetrical segregation coupled to normal checkpoints by careful analysis of multipolar endomitotic spindles: whereas each aster is connected to more than one other aster, one chromosome may segregate symmetrically between 2 spindle poles and still show asymmetrical segregation when the entire complex spindle is considered.

Anaphase↗
PubMed2001

Atlas of Genetics and Cytogenetics in Oncology and Haematology, updated.

The 'Atlas of Genetics and Cytogenetics in Oncology and Haematology' (http://www.infobiogen.fr/services/chromcancer) is an Internet database aimed at genes involved in cancer, cytogenetics and clinical entities in cancer, and cancer-prone diseases. It presents information in concise and updated reviews (cards) or longer texts (deep insights), a (new) case report section, a huge portal towards genetics and/or cancer databases, and teaching items in genetics for students in medicine and the sciences. This database is made for and by clinicians and researchers in the above-mentioned fields, who are encouraged to contribute. It deals with cancer research, genomics and cytogenomics. It is at the crossroads of research, post-university teaching and telemedicine. The Atlas is available at no cost.

Chromosome Aberrations↗
PubMed2001

Stromal cells and human malignant neuroblasts derived from bone marrow metastasis may share common karyotypic abnormalities: the case of the IGR-N-91 cell line.

BACKGROUND: Stage IV neuroblastoma is characterized by tumor invasion and metastatic dissemination. Cell lines derived from such neuroblastomas have a high in vitro proliferation capacity. PROCEDURE: We established three neuroblastoma cell lines derived from involved bone marrow of three patients with stage IV neuroblastoma and performed a cytogenetic study. RESULTS: Various culture conditions allowed us to distinguish two cell subpopulations: malignant neuroblasts (Nb-type) and substrate-adherent stromal cells (Str-type). Karyotypic analyses revealed two specific chromosomal abnormalities in diploid malignant IGR-N-331 neuroblasts, der(1)t(1;7)(p22;q11) and der(5)t(5;17)(q35;q21), one unbalanced translocation der(1)t(1;17)(p35;q21)x2 in hyperdiploid malignant IGR-N-337 neuroblasts, and a normal karyotype in both corresponding stromal subpopulations. In contrast, in the IGR-N-91 model, both cell types shared two unbalanced translocations, t(1;4)(q12;p15) and t(2;10)(p14;q11), suggesting that stromal cells and malignant neuroblasts originate from a common stem cell. CONCLUSIONS: Based on our findings, we postulate that genetically modified stromal cells may influence the metastatic potential of malignant neuroblasts.

Bone Marrow Cells↗
PubMed2001

In vivo elimination of acentric double minutes containing amplified MYCN from neuroblastoma tumor cells through the formation of micronuclei.

Neuroblastoma, the most common solid extracranial neoplasm in children, shows an appreciable variability in clinical evolution. Amplification of the MYCN oncogene in this tumor is detected in 25 to 30% of cases and is associated with poor clinical outcome. In this study, quantitative polymerase chain reaction and fluorescence in situ hybridization were used to determine MYCN amplification status in 46 neuroblastoma tumors. MYCN amplification was detected in tumors from 11 patients. Fluorescence in situ hybridization revealed the presence of micronuclei containing amplified MYCN sequences in 8 of the 11 tumors. Micronuclei are indicative of spontaneous elimination or loss of amplified sequences by tumor cells. Because the elimination of amplified sequences can be enhanced in vitro by specific drugs such as hydroxyurea, our observations suggest a new therapeutic strategy specifically targeted to cells with amplified genes.

Child, Preschool↗
PubMed2001

Chromosomal abnormalities in liver cell dysplasia detected by comparative genomic hybridisation.

BACKGROUND/AIM: The pathogenetic relation between liver cell dysplasia and hepatocellular carcinoma (HCC) is poorly understood. The aim of this study was to determine whether there is a genetic link between liver cell dysplasia and HCC that could support the role of dysplasia as a tumour precursor lesion. METHODS: Microdissection from paraffin wax embedded sections and degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) were combined to analyse chromosomal imbalances by comparative genomic hybridisation (CGH) in nine HCCs and nodules containing liver cell dysplasia and cirrhosis adjacent to the tumours. Seven cases of large cell changes (LCC) and three cases of small cell changes (SCC) were analysed. The genetic abnormalities detected in liver cell dysplasia were then compared with those present in the corresponding HCC. RESULTS: No abnormalities were detected in LCC and cirrhotic nodules, arguing against the preneoplasic nature of these cell foci. In contrast, a subset of chromosomal alterations present in HCCs was found in the adjacent SCC. CONCLUSIONS: These findings support the preneoplastic status of SCC in human hepatocarcinogenesis.

Carcinoma, Hepatocellular↗
PubMed2000

Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients.

To discriminate among the chromosomal abnormalities associated with the etiology of hepatocellular carcinoma (HCC), we performed a comparative genomic hybridization (CGH) analysis on 34 HCCs resected on non-cirrhotic livers from patients serologically negative for both hepatitis B (HBV) and C (HCV) viruses. The results were compared to those of a previous analysis of 50 HCCs selected on the basis of their positivity for HBV infection. The majority of the abnormalities found in the HBV positive cases (losses of chromosome arms 1p, 8p, 6q, 13q and 14q and gains of 1q, 8q, 6p and 17q) were similarly detected in the virus negative specimens. In contrast, a significant decrease (40% on average) was observed for losses at 4q, 16q and 17p in non-viral HCC samples, suggesting that these abnormalities are tightly associated with HBV infection. Thus, in addition to a common pathway towards malignancy, a subset of alterations may preferentially contribute to virus-induced carcinogenesis. In a parallel CGH study of 10 fibrolamellar carcinomas, a rare subtype of HCC, we found in six out of the seven informative cases, gains of chromosome arm 1q. This region, which is also preferentially amplified in non fibrolamellar tumors (58%), may contain an essential proto-oncogene commonly implicated in liver carcinogenesis.

Adolescent↗
PubMed2000

The "Atlas of genetics and cytogenetics in oncology and haematology" on the internet and a review on infant leukemias.

The "Atlas of Genetics and Cytogenetics in Oncology and Haematology" (URL: http://www.infobiogen.fr/services/chromcancer) is a database devoted to chromosome abnormalities in cancer, cancer-prone diseases, and genes involved in cancer. The information is concise and updated. This database is made for and by cytogeneticists, molecular biologists, clinicians in oncology and hematology, and pathologists, who are encouraged to contribute. The database is herein presented, together with an example concerning congenital leukemias.

Child, Preschool↗
PubMed2000

Mapping of the 7q31 subregion common to the small chromosome 7 derivatives from two sporadic papillary renal cell carcinomas: increased copy number and overexpression of the MET proto-oncogene.

Molecular cytogenetic analysis of several sporadic papillary renal cell carcinomas and of their xenografts in immunodeficient mice had previously allowed us to delimit a minimal overrepresented region of chromosome 7 shared by all of them to band 7q31. We have refined the location of the overlapping region to the junction of the subbands 7q31.2 and 7q31.3 by reverse painting with two differently labelled probes prepared from the small chromosome 7 derivatives microdissected from the cells of two distinct tumours. This small region was shown to contain the MET proto-oncogene, present at three to four copies per cell as determined by Southern blot analysis. The increased copy number of the MET gene was found to be associated with its overexpression at the mRNA level. However, no change in MET copy number or expression level was observed in the cells from two xenografted tumours serially transplanted into immunodeficient mice, as compared to those from the corresponding initial tumours. Our results indicate that expression of the MET proto-oncogene above a critical threshold is required for the maintenance of the tumorigenic phenotype of at least some papillary renal cell carcinomas, but does not further increase during tumour progression.

Animals↗
PubMed2000

Atlas of genetics and cytogenetics in oncology and haematology, an interactive database.

The 'Atlas of Genetics and Cytogenetics in Oncology and Haematology' (http://www.infobiogen.fr/services/chromcancer ) is a database devoted to chromosome abnormalities in cancer, cancer-prone diseases and genes involved in cancer. Information presented in each page is concise and updated. This database is made for and by: cytogeneticists, molecular biologists, clinicians in oncology and in haematology, and pathologists, who are encouraged to contribute.

Chromosome Aberrations↗
PubMed1999

Phenotypic and genotypic diversity of human neuroblastoma studied in three IGR cell line models derived from bone marrow metastases.

Metastatic stage IV neuroblastoma tumors, as well as cell lines derived from them, are highly malignant and rapidly fatal. To determine whether malignant potential of these cells might be influenced by stromal tissue at sites frequently involved in metastasis, we initiated primary cultures from bone marrow of three patients (331, 337, and 91) with stage IV neuroblastoma. All three explants contained two distinct cell populations, malignant neuroblasts (Nb-type) and substrate adherent stromal-like (Str-type) cells. The cell types were separated at the first passage and studied by cytogenetic, molecular, and immunocytochemical methods. Karyotypic analyses after 3-6 passages in vitro revealed the presence of unique chromosomal abnormalities in Nb-type cells of all three lines: (1) der(1)t(1;7) (p32;q11) and der(5)t(5;17)(q35;q21) in pseudodiploid IGR-N-331 neuroblasts; (2) der(1)t(1;17)(p35;q21-22) x 2 and der(7)t(7;7)(p21;q21) in IGR-N-337 hyperdiploid neuroblasts; and (3) more than six rearranged chromosomes in two related subpopulations of hypodiploid IGR-N-91 neuroblasts. Neuroblastic cells from all three tumors amplified MYCN 25- to 50-fold (with amplified genes visible as dmin or, in one IGR-N-91 subline, as an hsr(14)[q32]) and expressed N-CAM. Str-type cells from tumors 331 and 337 had a normal diploid karyotype, did not express either N-CAM or S-100, and are probably normal bone marrow fibroblasts. By contrast, S-100 negative Str-type IGR-N-91 cells were hypodiploid and shared at least two unbalanced translocations, der(4)t(1;4)(q12;p15) and der(2)t(2;10;17)(p14;q11;q22), with neuroblastic counterparts, indicating that "stromal" cells and malignant neuroblasts had a common tumor cell origin. Thus, the Str-type cells of IGR-N-91 are examples of S-type phenotypic variants frequently described for long-term human neuroblastoma cells lines in vitro, but not previously observed in vivo.

Bone Neoplasms↗
PubMed1999

Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma.

BACKGROUND: Gain of genetic material from chromosome arm 17q (gain of segment 17q21-qter) is the most frequent cytogenetic abnormality of neuroblastoma cells. This gain has been associated with advanced disease, patients who are > or =1 year old, deletion of chromosome arm 1p, and amplification of the N-myc oncogene, all of which predict an adverse outcome. We investigated these associations and evaluated the prognostic importance of the status of chromosome 17. METHODS: We compiled molecular cytogenetic analyses of chromosome 17 in primary neuroblastomas in 313 patients at six European centers. Clinical and survival information were collected, along with data on 1p, N-myc, and ploidy. RESULTS: Unbalanced gain of segment 17q21-qter was found in 53.7 percent of the tumors, whereas the chromosome was normal in 46.3 percent. The gain of 17q was characteristic of advanced tumors and of tumors in children > or =1 year of age and was strongly associated with the deletion of 1p and amplification of N-myc. No tumor showed amplification of N-myc in the absence of either deletion of 1p or gain of 17q. Gain of 17q was a significant predictive factor for adverse outcome in univariate analysis. Among the patients with this abnormality, overall survival at five years was 30.6 percent (95 percent confidence interval, 21 to 40 percent), as compared with 86.0 percent (95 percent confidence interval, 78 to 91 percent) among those with normal 17q status. in multivariate analysis, gain of 17q was the most powerful prognostic factor, followed by the presence of stage 4 disease and deletion of 1p (hazard ratios, 3.4, 2.3, and 1.9, respectively). CONCLUSIONS: Gain of chromosome segment 17q21-qter is an important prognostic factor in children with neuroblastoma.

Analysis of Variance↗
PubMed1999

Molecular cloning, expression analysis, and chromosomal localization of human syntaxin 8 (STX8).

We report the cloning of a cDNA encoding human syntaxin 8 (STX8), using the regulator (R) domain of the cystic fibrosis transmembrane conductance regulator (CFTR) as a bait to screen a human fetal lung cDNA library by the yeast two-hybrid system. This gene was found broadly transcribed and its mRNA size is about 1.3 kb. The STX8 gene maps to chromosomal band 17p12 and it encodes a 236-amino-acid protein. Syntaxin 8 contains in its C-terminal half a coiled-coil domain found highly conserved in the t-SNARE (SNAP receptor on target membrane) superfamily of proteins, which are involved in vesicular trafficking and docking. In syntaxin 8, a C-terminal hydrophobic domain may constitute a transmembrane anchor. It was recently shown that CFTR-mediated chloride currents can be regulated by syntaxin 1A, a t-SNARE family member, through direct protein-protein interaction. This raises the possibility that syntaxin 8 may also be involved in such regulations.

Amino Acid Sequence↗
PubMed1999

A database on cytogenetics in haematology and oncology.

The aim of 'Atlas of Genetics and Cytogenetics in Oncology and Haematology' (http://www.infobiogen.fr/services/chromcancer) is to present summarized information on chromosome abnormalities in cancer, with extensions to genes involved in cancer and to cancer-prone diseases. Information is to be updated. This database is made for and by cytogeneticists, molecular biologists, clinicians in oncology and in haematology, and pathologists.

Chromosome Aberrations↗