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C M Croce

Publications and source records attributed to C M Croce.

At least 307 records · Page 17Linked to original sources
PubMed1987

Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas.

The chromosomal locations of cellular sequences flanking integrated papillomavirus DNA in four cervical carcinoma cell lines and a primary cervical carcinoma have been determined. The two human papillomavirus (HPV) 16 flanking sequences derived from the tumor were localized to chromosome regions 20pter----20q13 and 3p25----3qter, regions that also contain the protooncogenes c-src-1 and c-raf-1, respectively. The HPV 16 integration site in the SiHa cervical carcinoma-derived cell line is in chromosome region 13q14----13q32. The HPV 18 integration site in SW756 cervical carcinoma cells is in chromosome 12 but is not closely linked to the Ki-ras2 gene. Finally, in two cervical carcinoma cell lines, HeLa and C4-I, HPV 18 DNA is integrated in chromosome 8, 5' of the c-myc gene. The HeLa HPV 18 integration site is within 40 kilobases 5' of the c-myc gene, inside the HL60 amplification unit surrounding and including the c-myc gene. Additionally, steady-state levels of c-myc mRNA are elevated in HeLa and C4-I cells relative to other cervical carcinoma cell lines. Thus, in at least some genital tumors, cis-activation of cellular oncogenes by HPV may be involved in malignant transformation of cervical cells.

Attachment Sites, Microbiological↗
PubMed1987

DNA rearrangements in human follicular lymphoma can involve the 5' or the 3' region of the bcl-2 gene.

In most human follicular lymphomas, the chromosome translocation t(14;18) occurs within two breakpoint clustering regions on chromosome 18, the major one at the 3' untranslated region of the bcl-2 gene and the minor one at 3' of the gene. Analysis of a panel of follicular lymphoma DNAs using probes for the first exon of the bcl-2 gene indicates that DNA rearrangements may also occur 5' to the involved bcl-2 gene. In this case the IgH locus and the bcl-2 gene are found in the order 3' C gamma S gamma/mu JH 5'::5' bcl-2 3' (where C = constant, S = switch, and JH = joining segment of the heavy chain locus), suggesting that an inversion also occurred during the translocation process. The coding regions of the bcl-2 gene, however, are left intact in all cases of follicular lymphoma studied to date.

Base Sequence↗
PubMed1987

MYC oncogene involved in a t(8;22) chromosome translocation is not altered in its putative regulatory regions.

We have cloned the translocation-associated MYC gene from the Burkitt lymphoma cell line (BL2) with a t(8;22) chromosomal translocation and have determined the nucleotide sequence of the first exon and of the 3' and 5' flanking regions, where sequences with putative regulatory functions have been identified. The nucleotide sequence of the 5' flanking region, which contains regions of DNase hypersensitivity and binding sites for putative regulatory proteins, is the same as that of the normal MYC. Accordingly, mutations in these regulatory regions are not required for the transcriptional deregulation of MYC in the BL2 cell line. The nucleotide sequence of the first exon is similar to that of the normal MYC [Gazin, C., Dupont de Direchin, S., Hampe, A., Masson, J. M., Martin, P., Stehelin, D. & Galibert, F. (1984) EMBO J. 3, 383-387] and has the coding capacity for a 188-residue polypeptide. However, six nucleotide changes that occur in the middle of this reading frame could result in amino acid substitutions. We also have cloned and sequenced the t(8;22) chromosomal breakpoint that is located 10 kilobases 3' of the MYC exon 3 and near the C lambda 3 gene on chromosome 22. Sequences with homology to immunoglobulin joining signals occur close to the breakpoint both on chromosome 8 and 22, providing further evidence that the immunoglobulin joining enzymes may be involved in the recombinations associated with a variety of chromosomal translocations in B and T cells.

Amino Acid Sequence↗
PubMed1987

Molecular mechanisms of chromosome translocation in human B- and T-cell neoplasia.

Our understanding of the molecular biology of many tumors is still rudimentary. The genes involved in most solid tumors, and the mechanisms giving rise to their activation, are virtually unknown. In contrast, for hematopoietic malignancies, we have identified several genes important in oncogenesis, and we understand in at least a limited sense the mechanisms by which translocations impart these genes with the capacity to support malignant growth. It is becoming increasingly apparent that these mechanisms involve very subtle changes in the pattern of gene expression. Similarly, the studies on the mechanisms of chromosome translocation described here underscore the proposition that malignancy may arise by slight perturbations of normal function. The enzymes that physiologically recombine Ig and TCR genes do so with high fidelity under normal circumstances. But occasionally misrecognition of target sequences may lead to chromosome translocation and neoplasia. A deeper understanding of this process will be facilitated by a more certain grasp of normal B- and T-lymphocyte differentiation and proliferation.

B-Lymphocytes↗
PubMed1987

Human homeo box-containing genes located at chromosome regions 2q31----2q37 and 12q12----12q13.

Four human homeo box-containing cDNAs isolated from mRNA of an SV40-transformed human fibroblast cell line have been regionally localized on the human gene map. One cDNA clone, c10, was found to be nearly identical to the previously mapped Hox-2.1 gene at 17q21. A second cDNA clone, c1, which is 87% homologous to Hox-2.2 at the nucleotide level but is distinct from Hox-2.1 and Hox-2.2, also maps to this region of human chromosome 17 and is probably another member of the Hox-2 cluster of homeo box-containing genes. The third cDNA clone, c8, in which the homeo box is approximately 84% homologous to the mouse Hox-1.1 homeo box region on mouse chromosome 6, maps to chromosome region 12q12----12q13, a region that is involved in chromosome abnormalities in human seminomas and teratomas. The fourth cDNA clone, c13, whose homeo box is approximately 73% homologous to the Hox-2.2 homeo box sequence, is located at chromosome region 2q31----q37. The human homeo box-containing cluster of genes at chromosome region 17q21 is the human cognate of the mouse homeo box-containing gene cluster on mouse chromosome 11. Other mouse homeo box-containing genes of the Antennapedia class (class I) map to mouse chromosomes 6 (Hox-1, proximal to the IgK locus) and 15 (Hox-3). A mouse gene, En-1, with an engrailed-like homeo box (class II) and flanking region maps to mouse chromosome 1 (near the dominant hemimelia gene). Neither of the class I homeo box-containing genes--c8 and c13--maps to a region of obvious homology to chromosomal positions of the presently known mouse homeo box-containing genes.

Cell Line↗
PubMed1987

Characterization of the protein product of bcl-2, the gene involved in human follicular lymphoma.

A protein corresponding in size to the bcl-2 alpha protein obtained after in vitro transcription and in vitro translation in a rabbit reticulocyte lysate was specifically immunoprecipitated from a human B-cell extract using rabbit polyclonal antiserum raised against a beta-galactosidase/bcl-2 fusion protein. Peptide mapping with V8 protease confirmed the identity of this protein as human bcl-2 alpha. Subcellular fractionation of cellular protein followed by immunoprecipitation showed that the bcl-2 alpha protein is associated with the cell membrane.

B-Lymphocytes↗
PubMed1987

Characterization of the human PIM-1 gene: a putative proto-oncogene coding for a tissue specific member of the protein kinase family.

The mouse PIM-1 gene is involved in the pathogenesis of virally-induced mouse lymphomas. We have cloned and analyzed the human homologue of the mouse PIM-1 gene to investigate its role in human lymphoma and leukemia. Overlapping cDNA clones from a K562 (human erythroleukemia cell line) library were isolated and sequenced. The deduced amino acid sequence showed significant homology to a number of the protein kinases but did not have a transmembrane region. Genomic clones from the 380 cell line (human B cell leukemia) were analyzed. The PIM-1 transcript was found to derive from 5 Kb of genomic DNA. Six exons and five introns were identified. The promoter region has no TATA or CAAT boxes, but did have multiple potential Sp1 binding sites (CCGCCC). Studies of expression of this gene using Northern blots of human cell lines showed it to be transcribed primarily in B lymphoid and myeloid cell lines. The characterization of the human PIM-1 gene will allow the definition of its role in hemopoietic malignancies and in hematolymphoid differentiation.

Amino Acid Sequence↗
PubMed1987

Oncogene probes in the detection of human cancer.

Specific chromosomal translocations are involved in more than 80% of human B cell neoplasms. In all these cases, the neoplastic phenotype is apparently the consequence of reciprocal chromosomal translocations involving the loci for human immunoglobulin chains and either well-described cellular protooncogenes or putative protooncogenes. The juxtaposition of the protooncogenes to the immunoglobulin loci results in their transcriptional deregulation, because of their proximity to genetic elements within the human immunoglobulin loci capable of activating gene transcription in cis over considerable chromosomal distances. Sequence analysis of the translocation breakpoints has provided important insights concerning the molecular mechanisms involved in chromosome translocation in B cells. It appears that the reciprocal translocations contributing to B cell neoplasia are catalyzed by the same enzymes that are involved in physiological immunoglobulin gene rearrangements. The analysis of human B cell leukemias and lymphomas has also provided considerable information concerning the possible scenarios for B cell neoplastic transformation. It is clear that the Epstein-Barr virus does not play a direct role in neoplastic transformation, but it may contribute by increasing the number of B cells at risk of developing chromosome translocations during immunoglobulin gene rearrangements. Cytogenetic and molecular genetic analysis of T cell malignancies is beginning to provide a very similar scenario for neoplastic transformation. The locus for the alpha-chain of the T cell receptor is directly involved, and it apparently juxtaposes to protooncogenes or to putative protooncogenes leading to their transcriptional deregulation. It seems quite likely that the enzyme system involved in rearrangements of the genes for the T cell receptor plays a crucial role in the causation of these chromosomal translocations. Thus, the genetic basis of many human B and T cells may be quite similar. For the future, the challenge resides in trying to characterize specifically the role of both old and new protooncogenes in B and T cell proliferation, normal and neoplastic.

Genes↗
PubMed1986

A common mechanism of chromosomal translocation in T- and B-cell neoplasia.

The chromosomal breakpoint involved in the t(8;14)(q24;q11) chromosome translocation in the SKW-3 cell line, which directly involves the 3' flanking region of the c-myc gene, was cloned and sequenced. The breakpoint on chromosome 8 mapped to a position 3 kb 3' of c-myc while the chromosome 14 breakpoint occurred 36 kb 5' of the gene for the constant region of the alpha chain of the T-cell receptor (TCR). The translocation resulted in a precise rearrangement of sequences on chromosome 8 and what appears to be a functional J alpha segment on chromosome 14. Signal sequences for V-J joining occurred at the breakpoint positions on both chromosomes 14 and 8, suggesting that the translocation occurs during TCR gene rearrangement and that it is catalyzed by the enzymatic systems involved in V-J joining reactions. The involvement of c-myc in the translocation and the association of joining signals at the breakpoints provides a parallel to the situation observed in the translocations involving c-myc and the immunoglobulin loci in B-cell neoplasms and suggests that common mechanisms of translocation and oncogene deregulation are involved in B- and T-cell malignancies.

B-Lymphocytes↗
PubMed1986

Analysis of the 3' flanking region of the human c-myc gene in lymphomas with the t(8;22) and t(2;8) chromosomal translocations.

We have cloned and mapped the sequences extending 38 kb 3' of the c-myc gene. This region is found to be highly repetitive in nature and hybridizes extensively with a BLUR 8 Alu probe. Unique sequence probes derived from this region were used to map the chromosomal breakpoints of a number of lymphoma cell lines with t(2;8) or t(8;22) translocations. In five of the cell lines (PA682, LY67, LY47, LY66 and LY91), the immunoglobulin light chain locus translocates into a region which is greater than 47 kb downstream of c-myc. For one of the cell lines, JI, the location of the breakpoint on the 8q+ chromosome was found to be 25-32 kb 3' of c-myc. The breakpoint for the BL2 cell line had been previously mapped at 10 kb 3' of the c-myc oncogene. Analyses of steady-state levels of c-myc mRNA in cell lines with chromosomal breakpoints ranging from 10 kb to greater than 47 kb 3' of c-myc range from 0.5 to 10X the levels in lymphoblast controls. The different levels of c-myc transcripts is not a direct function of the distance between the c-myc gene and the translocated immunoglobulin light chain locus.

Cell Line↗
PubMed1986

Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias.

Two human T-cell leukemias carrying a t(8;14)(q24;q11) chromosome translocation were studied for rearrangements and expression of the c-myc oncogene. For one leukemia, rearrangement was detected in a region immediately distal (3') to the c-myc locus; no rearrangements of c-myc were observed in the second case (DeF). However, studies with hybrids between human and mouse leukemic T cells indicated that in the leukemic cells of DeF, the breakpoint in chromosome 14 occurred between genes for the variable (V alpha) and the constant (C alpha) regions for the alpha chain of the T-cell receptor. The C alpha locus had translocated to a region more than 38 kilobases 3' to the involved c-myc oncogene. Since human c-myc transcripts were expressed only in hybrids carrying the 8q+ chromosome but not in hybrids containing the normal chromosome 8, it is concluded that the translocation of the C alpha locus 3' to the c-myc oncogene can result in its transcriptional deregulation.

Animals↗
PubMed1986

Isolation and partial characterization of a 48-kDa protein which is induced in normal lymphocytes upon mitogenic stimulation.

A 48-kDa protein (p48) crossreactive with an antiserum directed against the 12 C-terminal amino acids of the human cellular myc gene-encoded protein was isolated from a Burkitt lymphoma cell line. The p48 protein is a basic protein and has a cytoplasmic localization. An antiserum prepared against purified p48 reacts specifically with a 48-kDa protein present in a variety of mouse and human cells. This polypeptide is detected at very low levels in normal, resting, peripheral blood lymphocytes, but is induced several-fold by stimulation with either concanavalin A or pokeweed mitogen. The association of p48 induction with a proliferative response and the crossreactivity with the cellular myc protein are discussed.

Animals↗
PubMed1986

Translocation breakpoint mapping: molecular and cytogenetic studies of chromosome 22.

A number of clinically significant human diseases are associated with rearrangements of chromosome #22. These include the t(9;22) of chronic myelogenous leukemia (CML), the t(8;22) of Burkitt's lymphoma (BL), the t(11;22)(q23;q11) constitutional rearrangement and the t(11;22) of Ewing's sarcoma (ES) and neuroepithelioma (NE). All of these translocations have breakpoints in 22q11. Using a molecular cytogenetic approach and various cloned portions of the lambda light chain gene as probe, we have assigned a linear order within 22q11 to these breakpoints. Using chromosomal in situ hybridization we have determined that the 22q11 breakpoint in BL2, a t(8;22) Burkitt's lymphoma is proximal to the breakpoint of the t(9;22) of CML. We have demonstrated that the 22q11 breakpoint of PA682, another t(8;22) BL cell line, interrupts the lambda light chain locus. Using a combination of variable and constant region probes and PA682 cells, we have shown that the lambda light chain locus is oriented such that V lambda is proximal to C lambda in 22q11. Our results for the constitutional t(11;22) indicate that the 22q11 breakpoint is distal to that of BL, proximal both to that of CML and ES and, in addition, it interrupts the C lambda gene cluster. Our studies of the 22q11 breakpoint of the t(11;22) of ES and NE suggest that they are the most distal of the breakpoints we studied on chromosome #22.

Burkitt Lymphoma↗