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C Bastard

Publications and source records attributed to C Bastard.

At least 73 records · Page 4Linked to original sources
PubMed1994

Molecular cloning of a t(11;14)(q13;q32) translocation breakpoint centromeric to the BCL1-MTC.

In B-cell malignancies, the t(11;14)(q13;q32) at the 11q13 BCL1 locus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between the BCL1 major translocation cluster (MTC) and the PRAD1 (also termed cyclin D1 or CCND1) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric to PRAD1. We report here the molecular cloning of a new t(11;14) breakpoint site, 20 kb centromeric to the MTC, from a patient with prolymphocytic leukemia. We subcloned a non-repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHO11c) relative to already identified breakpoint sites, using long- and short-range physical mapping within the BCL1 locus. Rearrangements in the BCL1 locus are associated with deregulation of the PRAD1 gene, which is often overexpressed, particularly in mantle-cell malignancies. The detectable but weak PRAD1 expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCL1 locus boundaries. We think that attention should be focused on this region centromeric to the BCL1-MTC, where the investigation of previously unidentified translocations may increase understanding of the PRAD1 gene deregulation in t(11;14) associated pathologies.

Adult↗
PubMed1994

Genetic study of dopamine D1, D2, and D4 receptors in schizophrenia.

The goal of this study was to define precisely the involvement of the dopamine D1, D2, and D4 receptor genes in the etiology of schizophrenia. A linkage analysis using the lod score method was performed in 37 families originating from France (n = 14) and from the Island of La Réunion in the Indian Ocean (n = 23). No evidence of linkage between schizophrenia and genetic markers located at these loci was found. A simulation study was carried out to gauge the significance of these results. The conclusions of a nonparametric linkage test (i.e., the affected pedigree member method) were equally negative. For each genetic marker, an allelic association with the disease was also sought: 80 unrelated patients and 80 healthy control subjects were tested, and no significant association was found. These results, which are in agreement with those obtained by other groups, do not support the involvement of the dopamine D1, D2, and D4 receptor genes in the pathogenesis of schizophrenia.

Female↗
PubMed1994

Pseudoautosomal region in schizophrenia: linkage analysis of seven loci by sib-pair and lod-score methods.

In a previous study, we reported a nonrandom segregation between schizophrenia and the pseudoautosomal locus DXYS14 in a sample of 33 sibships. That study has been extended by the addition of 16 new sibships from 16 different families. Data from six other loci of the pseudoautosomal region and of the immediately adjacent part of the X specific region have also been analyzed. Two methods of linkage analysis were used: the affected sibling pair (ASP) method and the lod-score method. Lod-score analyses were performed on the basis of three different models--A, B, and C--all shown to be consistent with the epidemiological data on schizophrenia. No clear evidence for linkage was obtained with any of these models. However, whatever the genetic model and the disease classification, maximum lod scores were positive with most of the markers, with the highest scores generally being obtained for the DXYS14 locus. When the ASP method was used, the earlier finding of nonrandom segregation between schizophrenia and the DXYS14 locus was still supported in this larger data set, at an increased level of statistical significance. Findings of ASP analyses were not significant for the other loci. Thus, findings obtained from analyses using the ASP method, but not the lod-score method, were consistent with the pseudoautosomal hypothesis for schizophrenia.

Family↗
PubMed1994

Heterogeneity in B-cell neoplasms associated with rearrangement of the LAZ3 gene on chromosome band 3q27.

The LAZ3 gene has been identified on chromosome band 3q27, which is the breakpoint of reciprocal chromosome translocations observed in B-cell non-Hodgkin's lymphoma (NHL). Although the translocations affect various chromosome sites including the immunoglobulin gene loci, molecular studies have indicated that the breakages are clustered within a 10-kb-long major translocation cluster region (MTC) at band 3q27. In the current study, we have used a genomic probe from the MTC to study 51 Japanese patients having B-cell neoplasms with regard to rearrangement of LAZ3. The study detected rearrangement in 12 cases out of 51; the rearrangements occurred within a limited region close to the first exon of the LAZ3 gene. Eight cases out of 12 with rearrangement had diffuse large cell NHL and the immunoblastic variant, including one case transformed from a follicular lymphoma carrying the BCL2 rearrangement. However, the rearrangement was also identified in two NHL patients showing a follicular growth pattern, in one case with indolent chronic lymphocytic leukemia and in one case with high-grade small noncleaved cell lymphoma with a bulky abdominal mass. Cytogenetic analysis revealed t(3;14)(q27;q32) in 2 cases, t(3;22)(q27;q11) in 3, and a newly identified translocation t(3;6)(q21) in one case. LAZ3 expression was demonstrated in cells carrying the LAZ3 rearrangement, suggesting transcriptional deregulation of the gene. Our results are compatible with previous cytogenetic reports in which the 3q27 translocation was observed in 15-20% of NHL; however, patients with the LAZ3 rearrangements exhibited a wide range of clinico-pathologic characteristics. Thus, there is no clear consistent association of the 3q27 translocation with a specific subtype of B-cell neoplasm.

Adult↗
PubMed1993

Expanded range of 11q13 breakpoints with differing patterns of cyclin D1 expression in B-cell malignancies.

We have analyzed the BCL1 locus in a series of 24 B-cell tumors and cell lines with rearrangements of 11q13 (mostly t(11;14)(q13;q32) translocations). Using Southern hybridization and/or fluorescence in situ hybridization (FISH) on metaphase chromosomes, we have not only confirmed the scattering of the breakpoints between the BCL1 locus and the cyclin D1 gene (CCND1), but also shown that some of the breakpoints could be as far as 500 kb on either side of the latter. Expression of CCND1 was not restricted to cases with t(11;14)(q13;q32), but was also associated with other 11q13 rearrangements, such as a t(8;11)(p22;q13). Whatever the alteration at 11q13, a correlation was observed between the expression of CCND1 and the presence of a breakpoint within 150 kb upstream of the gene. On the contrary, three samples, including a bona fide t(11;14) translocation and two cases with breakpoints located outside the BCL1-CCND1 area, did not exhibit detectable levels of CCND1 transcripts. Our results raise the possibility that several discrete molecular events can take place at 11q13 in B-cell malignancies.

Base Sequence↗
PubMed1993

Cloning of a breakpoint cluster region at band 3q27 involved in human non-Hodgkin's lymphoma.

In a previous cytogenetic analysis, we showed the recurrence of translocations involving band 3q27 and immunoglobulin gene regions in 20 out of 319 patients with non-Hodgkin's lymphoma (NHL). We report here the molecular cloning of the translocation breakpoint from tumor cells of a patient (LAR) with t(3;14)(q27;q32) and the isolation of DNA probes which identify a major translocation cluster region (MTC) at band 3q27. A DNA library from LAR tumor cells was screened with a JH probe and several clones were identified corresponding either to a somatic rearrangement of JGH genes (V4-D2-J6-C mu clonal rearrangement) or to the t(3;14). Analysis of the t(3;14) breakpoint showed that chromosome 3 material was translocated to an inverted 14q32 VH-containing fragment which was itself translocated to the J3 gene. Chromosome 3-assigned probes were used to investigate local DNA rearrangements in a series of NHL with 3q27 translocations. Rearrangements were detected in 13 of 17 patients including 9 of 11 with t(3;14)(q27;q32), 1 of 2 with t(2;3)(p12;q27), 1 of 2 with t(3;22)(q27;q11), and 2 of 2 NHL with translocations not involving an IG gene, namely, t(3;4)(q27;p11) and t(3;7)(q27;p12). The finding of this MTC should be useful for diagnostic and prognostic studies and for the identification of a novel oncogene at band 3q27 involved in the development of B cell NHL.

Base Sequence↗
PubMed1993

LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas.

We have shown previously that chromosomal translocations involving chromosome 3q27 and immunoglobulin gene regions are the third most common specific translocations in non-Hodgkin's lymphoma (NHL). We now report the isolation of a gene that is disrupted in two cases by t(3;14) and t(3;4) translocations. The gene (LAZ3) encodes a 79 kDa protein containing six zinc-finger motifs and sharing amino-terminal homology with several transcription factors including the Drosophila tramtrack and Broad-complex genes, both of which are developmental transcription regulators. LAZ3 is transcribed as a 3.8 kb message predominantly in normal adult skeletal muscle and in several NHL carrying 3q27 chromosomal defects. We suggest that it may act as a transcription regulator and play an important role in lymphomagenesis.

Amino Acid Sequence↗
PubMed1993

Standardized nested polymerase chain reaction-based assay for detection of human immunodeficiency virus type 1 DNA in whole blood lysates.

The routine detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA in clinical samples requires a standardized, simple, and sensitive test. To identify the HIV-1 proviral DNA in blood, we used a solid-phase assay based on the affinity capture and the gamma counting of the amplified product after a nested polymerase chain reaction (AMPLICIS test). In order to simplify the general process, whole-blood lysates rather than peripheral blood mononuclear cell lysates were used for the amplifications. The solid-phase capture and counting of the final amplified products allowed us to define precise interpretive criteria to determine the positivity level of the test. Three new primer sets located in the gag and pol structural genes and in the tat regulatory gene of HIV-1 were studied. The results obtained in 54 seropositive and 120 seronegative individuals demonstrated the ability of the AMPLICIS test to be used for HIV-1 provirus detection: 53 of 54 of the seropositive specimens were found to be positive with at least two primer sets. We also assessed the usefulness of this test for the estimation of the HIV-1 DNA load by the end point dilution method with serial dilutions of blood lysates from 26 HIV-1-seropositive patients.

Base Sequence↗
PubMed1993

Translocation t(3;22)(q27;q11) in non-Hodgkin's malignant lymphoma: chromosome painting and molecular studies.

Translocation t(3;22)(q27;q11) has recently been recognized as a recurrent abnormality in non-Hodgkin's malignant lymphoma (NHL). A new gene, LAZ3, has been shown to be involved in NHL with 3q27 rearrangement. Two patients with B-cell NHL were studied by chromosome painting and Southern blot analysis. Fluorescence in situ hybridization to metaphase chromosomes was shown to be an easy way to detect the chromosomal abnormality even in metaphase cells with poorly defined chromosomes. The gene LAZ3 was rearranged in one patient in the 'major translocation cluster region'. The comigration of rearranged LAZ3 and of IGL bands suggests that the translocation resulted in the juxtaposition of the two genes. This juxtaposition makes possible a potential deregulation of the LAZ3 gene expression, as previously shown for the MYC and BCL2 genes in Burkitt and follicular lymphoma translocations.

Aged↗
PubMed1992

Translocations involving band 3q27 and Ig gene regions in non-Hodgkin's lymphoma.

We report a series of 20 non-Hodgkin's lymphomas (NHL) in which cytogenetic analysis showed a translocation involving band 3q27 and the site of one of the three Ig genes (14q32, 2p12, 22q11) in the neoplastic cells. These cases were found in a series of 319 patients with clonal chromosomal abnormalities studied over a 7-year period. Fourteen patients had diffuse lymphoma, mainly of large cell type and the remaining six were follicular lymphomas. All cases studied were of B-cell phenotype. A t(3;14)(q27;q32) was commonest, found in 15 patients (4.7%), with the two variant translocations, t(3;22)(q27;q11) and t(2;3)(p12;q27), being found in three and two patients, respectively. Additional chromosomal defects were present in most patients, but two patients had this type of translocation as the sole abnormality. These results indicate that translocations involving band 3q27 and Ig genes are not uncommon, and suggest that a novel oncogene, located at band 3q27, may be implicated in B-cell NHL.

Adult↗
PubMed1992

Molecular analysis of 12 patients with the t(8;21) translocation and M2 acute myelogenous leukemia.

The t(8;21)(q22;q22) is a nonrandom cytogenetic abnormality associated with acute myelogenous leukemia of the M2 subtype (FAB classification). The 8q- and 21q+ derivative chromosomes have previously been isolated in somatic cell hybrids and used to map the anonymous sequences D21S65 and D21S17, which were proximal and distal, respectively, to the breakpoint on chromosome 21. DNA from a series of 12 t(8;21) patients and 7 controls was analyzed by pulsed field gel electrophoresis. Physical linkage of probes D21S65 and D21S17 on a 2100 kb NruI fragment was established by partial digestion experiments. In all the patients, the translocation generated a rearranged D21S65 NruI fragment of 650 to 750 kb, suggesting heterogeneity in the breakpoints. This heterogeneity was confirmed by using BssHII, SacII, and EagI enzymes. Our results are consistent with the presence of a 100 Kb breakpoint cluster region on chromosome 21 encompassing the AML1 gene. Interestingly, in half of the patients, demethylation of an NruI site located 7 kb proximal to the last exon of the AML1 gene occurred on the nontranslocated chromosome 21.

Adolescent↗
PubMed1992

Localization of 11q13 loci with respect to regional chromosomal breakpoints.

We have employed two strategies to map 13 markers located at 11q13. First, we used pulsed-field gel electrophoresis of DNA fragments obtained with methylation-sensitive restriction enzymes. The markers used in this study were scattered over 8.4 Mb and, for most of them, could not be linked one to another. A second mapping strategy employed hybridization to either DNA of somatic hybrids containing various parts of the long arm of chromosome 11 or metaphase chromosomes of a B-cell line containing the t(11;14)(q13;q32) translocation. We were able to sort out the centromeric from the telomeric probes with respect to translocation breakpoints taken as reference chromosomal landmarks by this approach. BCL1, which corresponds to the region where the t(11;14)(q13;q32) translocation breakpoints are clustered, appears as a boundary between two areas of human/mouse homology present in conserved syntenic regions on mouse chromosomes 7 and 19.

Animals↗
PubMed1992

Establishment and characterisation of a human glioma cell line.

A new cell line, CB109, has been established from a human glioblastoma multiforme. The cytoskeleton was positive for glial fibrillary acidic protein, vimentin and fibronectin. Hyaluronan (HA) and the HA-binding protein hyaluronectin (HN) were expressed in the cell cytoplasm and in the extracellular matrix of spheroids and plated cells. Hyaluronidase did not prevent spheroid formation suggesting that HA was not involved in the cell-cell adhesion. HA precoating prevented cell adherence to the plates and favoured spheroid formation. HA was secreted in relatively large amounts into the culture medium. High performance liquid chromatography demonstrated that HA was in the high molecular weight form. The rate of HN secretion by cells was very low. Basic fibroblast growth factor significantly increased the proliferation in vitro and tumour growth after grafting into nude mice. The epidermal growth factor receptor was not expressed on cultivated CB109 cells. Cytogenetic analysis showed polysomy 7, structural rearrangement of chromosome 10 short arm and a translocation 13q13-q14 without detectable alteration of the RB gene.

Animals↗
PubMed1992

Evi-1 expression in leukemic patients with rearrangements of the 3q25-q28 chromosomal region.

The Evi-1 zinc-finger protein gene is normally not expressed in hematopoietic cells. However, high Evi-1 mRNA expression has been reported in mouse myeloblastic leukemias, due to transcriptional activation by proviral integration in either the Fim-3 or Evi-1 loci. The human Evi-1 gene is located on chromosome 3q24-q28. In this paper three examples are presented of human acute myelogenous leukemias presenting common characteristics: (i) high Evi-1 mRNA expression; (ii) chromosomal abnormalities t(3;3)(q21;q26) or inv(3;3)(q21-22;q26); and (iii) high platelet counts and dystrophic megakaryocytes. Thirty-four other patients with hematological malignancies, among which 11 had chromosomal rearrangements in the 3q24-q28 region did not exhibit such abnormalities. Of the 13 permanent hemopoietic cell lines tested, Evi-1 RNA expression was found in HEL and K-562 cell lines. Weak Evi-1 expression was also seen in fibroblasts and lung cells. This expression was affected neither in skin cells from a patient with a 3q27 constitutional translocation nor in a lung epithelioma cell line containing an excess of chromosome 3 long arm. Ectopic strong expression of Evi-1 in human leukemias could define an uncommon subclass of acute myelogenous leukemias with translocations involving the 3q25-28 chromosomal domain and abnormal megakaryopoiesis.

Adult↗
PubMed1991

Cytogenetic studies in untreated Hodgkin's disease.

Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11-13, 13p11-13, 3q26-28, 6q15-16, and 7q31-35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11-13 (P less than .01), 13p11-13 (P less than .01), 14p11 (P less than .01), 15p11-13 (P less than .02), and 20q12-13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12-13 (P less than .01) and 13p11-13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.

Adolescent↗