Search PubMed⌕ Search

Biomedical subjects

C Turc-Carel

Publications and source records attributed to C Turc-Carel.

At least 55 records · Page 3Linked to original sources
PubMed1994

The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts.

BACKGROUND: Precise diagnosis of small-round-cell tumors is often a challenge to the pathologist and the clinical oncologist. In Ewing's sarcomas and related peripheral primitive neuroectodermal tumors, a t(11;22) translocation or a (21,22) rearrangement is associated with hybrid transcripts of the EWS gene with the FLI1 or ERG gene. To investigate the diagnostic implication of this observation, we searched for these hybrid transcripts in tumors from patients with clinical and radiologic features of Ewing's sarcoma or peripheral primitive neuroectodermal tumors. METHODS: Samples of RNA from 114 tumors were reverse transcribed and subjected to the polymerase chain reaction with primers designed to amplify the relevant chimeric transcripts. All amplified products were sequenced. RESULTS: In-frame hybrid transcripts were observed in 89 cases. A hybrid transcript was found in 83 of 87 cases (95 percent) of Ewing's sarcoma or peripheral primitive neuroectodermal tumors. Samples of RNA from all of 12 tumors that had been proved to be other than Ewing's sarcoma or neuroectodermal tumors had no hybrid transcript. However, 6 of 15 undifferentiated tumors whose type was ambiguous (nonsecreting, poorly differentiated neuroblastoma or undifferentiated sarcoma) contained a hybrid transcript, suggesting that they might have to be reclassified. CONCLUSIONS: A subgroup of small-round-cell tumors identified as belonging to the Ewing family of tumors can be defined according to a specific molecular genetic lesion that is detectable by a rapid, reliable, and efficient method. This approach can be applied to small specimens obtained by fine-needle biopsies.

Adolescent↗
PubMed1994

Localization of the gene for DNA polymerase epsilon (POLE) to human chromosome 12q24.3 and rat chromosome 12 by somatic cell hybrid panels and fluorescence in situ hybridization.

DNA polymerase epsilon [DNA pol epsilon (EC 2.7.7.7)] is one of the four nuclear DNA polymerases in eukaryotic cells. The mammalian enzyme is involved in DNA repair and possibly also in replication of chromosomal DNA. The gene encoding pol epsilon (POLE) was assigned to human and rat chromosomes 12 by Southern blot analysis of genomic DNA from mouse-human and mouse-rat somatic cell hybrid panels using human cDNA probe. The human gene was then regionally localized to band 12q24.3 by fluorescence in situ hybridization of metaphase spreads of chromosomes from human lymphocytes using genomic DNA probe. POLE is closely linked to HNF1A, a gene encoding a liver-enriched transcription factor, HNF1 alpha. The two genes thus define a new synteny group retained on human and rat chromosomes 12. Another gene mapping to the same or close-by region as human POLE is a gene for inherited disorder tuberous sclerosis 3, TSC3.

Animals↗
PubMed1994

Comparative genomic hybridization as a tool to define two distinct chromosome 12-derived amplification units in well-differentiated liposarcomas.

Well-differentiated liposarcomas (WDLPS) are frequently characterized by a near-diploid karyotype with supernumerary ring and/or giant rod-shaped marker chromosomes. We have shown, using fluorescence in situ hybridization (FISH) and molecular strategies, that these markers contain chromosome 12-derived sequences. Here we report the analysis of six WDLPS for the presence of amplified DNA segments by means of the recently developed comparative genomic hybridization (CGH) strategy. Two distinct chromosome 12-derived amplification units could be identified in all tumors examined, one located in the q14-q15 region as expected, the second unexpectedly mapping to q21.3-q22. Our results indicate that the concerted amplification of these two distinct regions on the long arm of chromosome 12 may be a consistent characteristic of WDLPS. These amplifications are most likely directly related to the presence of supernumerary ring and/or giant marker chromosomes in this group of soft tissue tumors.

Cell Differentiation↗
PubMed1994

Mapping of the 12q12-q22 region with respect to tumor translocation breakpoints.

The consistent involvement of the region 12q13-q15 in numerous human tumors speaks in favor of the presence of genes that may contribute to oncogenesis. Mapping genes within this region of chromosome 12 is a necessary step toward the identification of those that play a role in this process. We have undertaken a multiplex analysis using translocation breakpoint mapping to order from the centromere to the telomere a series of 24 loci from the region 12q12-q22. Thirteen adipose tissue tumors with seven different chromosome changes involving the long arm of chromosome 12 (12q) were used. Since most of these loci are genes or anonymous DNA segments largely available to the scientific community, this map should be useful for investigation of genetic disorders associated with chromosome 12q. While these breakpoints were used as natural landmarks to order groups of loci, this work has positioned them more accurately, leading to a better chromosomal definition of the translocations than the one derived from standard cytogenetic studies.

Chromosome Mapping↗
PubMed1994

Molecular cloning of a putative novel human bZIP transcription factor on chromosome 17q22.

We have cloned and characterized cDNA clones representing several mRNA isoforms generated by alternative splicing of a single gene localized to chromosome 17q22. Sequence analysis showed that the predicted translational product of the longest open reading frame (2316 nucleotides, 772 amino acids) is related to transcription factors of the basic leucine zipper (bZIP) class. The sequence contained several regions characteristic of transcriptional regulatory domains. A cluster of amino acids flanking the bZIP region on both sides was highly conserved between TCF11 and p45 NF-E2, a subunit of the human globin locus control region-binding protein, NF-E2. These same regions showed remarkable homology to two invertebrate proteins, CNC and skin-1, postulated to regulate embryonic development in Drosophila melanogaster and Caenorhabditis elegans, respectively.

Amino Acid Sequence↗
PubMed1993

Chimeric EWS-FLI1 transcript in a Ewing cell line with a complex t(11;22;14) translocation.

Peripheral neuroectodermal tumors include the differentiated neuroepithelioma and the undifferentiated Ewing's tumor. Despite clinical and pathological differences, both malignancies are characterized by a t(11;22)(q24;q12) translocation which is observed in > 90% of the cases. Molecularly, the translocation is underlaid by a rearrangement between the EWS and Fli-1 genes on chromosomes 22 and 11, respectively. Because of the difficulties in the differential diagnosis between various small round cell tumors of childhood, including Ewing's tumor, a molecular diagnostic assay would be desirable. A prerequisite for predicting the reliability of such a test resides in the molecular elucidation of the peripheral neuroectodermal tumor cases which do not exhibit the prototypical translocation. We have analyzed one such case of Ewing's tumor-derived cell line with a t(11;22;14)(q24;q12;q11) translocation. An EWS-Fli-1 fusion transcript was evidenced by polymerase chain reaction amplification of a reverse transcription product obtained from total RNA. Direct sequencing was performed to demonstrate that the molecular rearrangement in this particular Ewing sample resulted in a fusion transcript similar to those observed in tumors with the prototypical translocation.

Base Sequence↗
PubMed1993

Combinatorial generation of variable fusion proteins in the Ewing family of tumours.

Balanced translocations involving band q12 of human chromosome 22 are the most frequent recurrent translocations observed in human solid tumours. It has been shown recently that this region encodes EWS, a protein with an RNA binding homologous domain. In Ewing's sarcoma and malignant melanoma of soft parts, translocations of band 22q12 to chromosome 11 and 12 result in the fusion of EWS with the transcription factors FLI-1 and ATF1, respectively. The present analysis of 89 Ewing's sarcomas and related tumours show that in addition to the expected EWS-FLI-1 fusion, the EWS gene can be fused to ERG, a transcription factor closely related to FLI-1 but located on chromosome 21. The position of the chromosome translocation breakpoints are shown to be restricted to introns 7-10 of the EWS gene and widely dispersed within introns 3-9 of the Ets-related genes. This heterogeneity generates a variety of chimeric proteins that can be detected by immuno-precipitation. On rare occasions, they may be associated with a truncated EWS protein arising from alternate splicing. All 13 different fusion proteins that were evidenced contained the N-terminal domain of EWS and the Ets domain of FLI-1 or ERG suggesting that oncogenic conversion is achieved by the linking of the two domains with no marked constraint on the connecting peptide.

Amino Acid Sequence↗
PubMed1992

In vitro karyotypic and immunophenotypic characterisation of primitive neuroectodermal tumours: similarities to malignant gliomas.

Monoclonal antibody (Mab) mediated immunotherapy of brain tumours requires the identification of tumour-restricted cell surface antigens. We have characterised four primitive neuroectodermal tumours, which included pineoblastoma, medulloblastoma and ependymoblastoma cultures, that demonstrated in vitro evidence of malignant behaviour (anchorage-independent growth and nu/nu xenograft tumour formation). The cytogenetic findings ranged from normal G-banded and Q-banded karyotypes through mixed near-diploid/hyperdiploid. These cultures resembled the cell surface immunophenotypic spectrum of malignant gliomas. They were distinguished from normal glia in vitro by the expression of restricted fetal mesenchymal, neuronal, myoblastic, melanocytic, epidermal, chondrocytic, lymphoid and epithelial antigens. Certain antigens appeared sufficiently represented among central nervous system (CNS) neoplasms to afford potential targets for Mab-mediated immunotherapy.

Adolescent↗
PubMed1992

Abnormal expression of neurofilament proteins in Ewing's sarcoma cell cultures.

A neural origin of Ewing's sarcoma (ES) has often been suggested and we have demonstrated neurofilament protein expression in ES cells. However, only the 200-kD subunit has been revealed in all of the ES cells analyzed. The 160- and 68-kD subunits were always absent. For these reasons, we have attempted to induce neural differentiation in 3 ES cell lines with different types of inducers: tetradecanoylphorbol-13-acetate (TPA) retinoic acid and nerve growth factor. When the cell lines were cultured for 7 days with TPA (10(-9) M) or retinoic acid (10(-7) M), only the 68-kD neurofilament subunit was slightly induced. No inducation was obtained when nerve growth factor was used, even at a 21-day culture. These results are in agreement with the putative neural origin of ES and may indicate an abnormal expression of neurofilament proteins in this tumor.

Cell Division↗
PubMed1991

Transfection of lipoma cells with papilloma bovine virus subgenomic fragment.

Lipoma cells with consistent chromosomal aberration have been transfected with plasmids carrying papilloma bovine virus subgenomic fragment (PBV 69). The successful transformation of the cells was ascerted on the changed growth pattern of the cells in liquid medium, colony formation in soft agar and modified cell appearance in electron microscopy; transfection with PBV 69 has not been, however, sufficient to immortalize lipoma cells.

Adipose Tissue↗
PubMed1990

Myxoid liposarcoma with t(12;16) (q13;p11) contains site-specific differences in methylation patterns surrounding a zinc-finger gene mapped to the breakpoint region on chromosome 12.

The q13 to q15 region of human chromosome 12 is frequently and consistently rearranged in malignant and benign adipose tissue tumors as well as benign tumors of smooth muscle and salivary glands. A reciprocal translocation, (12;16) (q13;p11), is characteristic of the myxoid subtype of liposarcoma, whereas translocations within 12q13-14 are frequently observed in benign lipomas. We are using pulsed-field gel electrophoresis to study the 12q13-q14 region in order to detect and clone the respective translocation breakpoints in these tumors. The locus GLI, which encodes a zinc-finger protein, has been mapped to the same region as the myxoid liposarcoma breakpoint. Pulsed-field analysis of myxoid liposarcoma and lipoma DNA has allowed us to construct a 600-kilobase physical map surrounding the GLI locus, which shows that breakpoints in both types of tumor are outside this region. However, myxoid liposarcoma DNA samples contained altered restriction fragments detectable with GLI probes that were highly specific and reproducible from case to case. These altered fragments are due to highly specific and reproducible methylation differences that are unique to myxoid liposarcoma DNA. These methylation changes may prove to be useful clinically as a diagnostic tool to differentiate subtypes of liposarcoma.

Cell Line↗
PubMed1989

Three possible cytogenetic subgroups of leiomyosarcoma.

Cytogenetic analysis was performed on short-term cultured tumor cells from ten patients diagnosed as having leiomyosarcoma. Of these, five tumors from five unrelated patients had clonal chromosome abnormalities. The combined data from this report and previous studies on leiomyosarcomas indicate that at least three subtypes may be identified chromosomally within leiomyosarcomas. One subtype is characterized by a hypodiploid chromosome number ranging from 41 to 43 and a common chromosome pattern of monosomies of chromosomes specific to this subgroup, including partial monosomy of the short arm of chromosome 1 (1p13----pter), monosomy 18, and consistent monosomy 22. In contrast to the previous subtype, for the pathogenesis of which the "tumor suppressor gene" hypothesis may be suggested, another subtype was characterized by a pseudodiploid chromosome number associated with simple reciprocal translocations; so far, these translocations are unique to individual tumors, the pathogenesis of which may involve a translocation-mediated gene deregulation pathway. A third subtype contained tumors with heterogeneous karyotypic findings.

Adult↗
PubMed1989

Immunologic characterization of Ewing's sarcoma using mesenchymal and neural markers.

The two most recent hypotheses about the histogenesis of Ewing's Sarcoma (ES) are that it has a mesenchymal or neuroectodermal origin. Immunologic markers specific to these two tissue origins were tested on cryostat sections from three primary tumors carrying the chromosomal translocation t(11;22)(q24;q12). Cell lines established in vitro from two of these three primary tumors were also analyzed. Using antibodies directed against neural components (neurone-specific-enolase [NSE], HNK-1, and neurofilament triplet proteins [NFTP]), positive reactions were observed in cells from two primary tumors and their corresponding cell lines. Results of electron microscopic examination of the primary tumors were compatible with the diagnosis of ES. When using antibodies directed against mesenchymal cell surface antigens (common leucocytes, Leu M1, Leu M2, and Leu M3), the weak positive reactions observed in the three primary tumors were attributed to lymphoid infiltrates within tumor cells. Six additional ES cell lines carrying the translocation t(11;22) were also analyzed by immunocytochemical and flow cytometry methods using antibodies directed against mesenchymal and neural components. Positive reactions were observed in all seven cell lines tested using antibodies directed against NSE, HNK-1, and 200 KD subunit of the NFTP, whereas negative reactions were obtained with Leu M2 antibody. These results are consistent with a neuroectodermal origin of ES cells.

Antibodies, Monoclonal↗