Biomedical subjects

L M Corcoran

Publications and source records attributed to L M Corcoran.

40 records · Page 3Linked to original sources

PubMed1984

Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion.

The myc oncogene is implicated here in T lymphocyte neoplasia. Cloning revealed a retroviral insert 0.7-1.3 kb 5' to c-myc in two T lymphomas induced by Soule murine leukemia virus and in a spontaneous T lymphoma ( Tikaut ) of an AKR mouse, a strain in which leukemogenesis involves recombinant retroviruses (MCF viruses). The tumor c-myc mRNAs appear normal but their level is approximately 5-fold higher than in most T lymphomas lacking c-myc rearrangement. Since each insert would be transcribed away from c-myc, its activation cannot involve the promoter of the long terminal repeat (LTR) but could reflect an enhancer, like that demonstrated within the Soule LTR. The Tikaut provirus has an MCF-like recombinant env gene and LTR sequence. MCF-like inserts were found near c-myc in seven of 31 other AKR T lymphomas; two lie 3' to c-myc and the five upstream are oriented away from c-myc. We conclude that a quarter of retrovirus-induced T lymphomas involve activation of c-myc, probably via the LTR enhancer.

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PubMed1983

Cellular myc oncogene is altered by chromosome translocation to an immunoglobulin locus in murine plasmacytomas and is rearranged similarly in human Burkitt lymphomas.

Molecular cloning has recently established that the 15;12 chromosome translocations in murine plasmacytomas fuse DNA from chromosome 15 to the immunoglobulin heavy (H) chain locus, usually within the switch recombination region near the alpha constant region gene. We show here that the incoming DNA bears the cellular gene (c-myc) homologous to the oncogene (v-myc) of avian retrovirus MC29. In human Burkitt lymphomas bearing an 8;14 translocation, c-myc was also rearranged, apparently (in at least two cases) to an H chain switch recombination region (mu or alpha), and both products of a reciprocal chromosome exchange were detectable. Both the murine and human c-myc genes contain two exons homologous to v-myc, and additional 5' and 3' murine genomic segments (apparent exons) were defined by hybridization to c-myc mRNAs. In plasmacytomas, chromosome breakpoints fall near or within the 5' exon and apparently disrupt the normal c-myc transcriptional unit, because plasmacytoma c-myc mRNAs differ from the mRNA in lines without c-myc rearrangement. The translocated gene presumably has lost its normal 5' regulatory sequences and may well encode an altered myc polypeptide. We propose that altered expression of the c-myc gene, induced by translocation to an immunoglobulin locus, is a critical oncogenic event for these B lymphoid tumors. Two events may be required, because the plasmacytoma oncogene capable of transforming fibroblasts is not c-myc.

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PubMedDate not supplied

Size variation in chromosomes from independent cultured isolates of Plasmodium falciparum.

The complexity of the life cycle of the protozoan malaria parasite Plasmodium falciparum has hindered genetic analysis; even the number of chromosomes in P. falciparum is uncertain. The blood stages of rodent malaria parasites are haploid and hybridization with cloned complementary DNAs similarly suggests a haploid genome in P. falciparum blood stages (ref. 4 and our unpublished results). A novel approach to karyoptic and linkage analysis in P. falciparum has been provided recently by the technique of pulsed-field gradient (PFG) gel electrophoresis, which allows the fractionation of DNA molecules of 30-3,000 kilobases (kb), a range including the sizes of intact chromosomal DNA molecules from eukaryotes such as yeast and trypanosomatids. We describe here the fractionation by PFG electrophoresis of chromosomal DNA molecules from P. falciparum into at least seven discrete species which vary in size by up to 20% between different isolates. Several genes for P. faciparum antigens which contain repetitive sequences are located on different chromosomes. Surprisingly, two of the chromosomes seem to contain the same sequences.

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PubMedDate not supplied

The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice.

Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin mu or kappa enhancer frequently develop a fatal lymphoma within a few months of birth. Since the tumours represent represent both immature and mature B lymphocytes, constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation. These myc mice should aid study of lymphoma development, B-cell ontogeny and immunoglobulin regulation.

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