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The human v-abl cellular homologue.

N Heisterkamp, J Groffen, J R Stephenson

    Journal of Molecular and Applied Genetics
    |January 1, 1983
    PubMed
    Summary
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    Researchers isolated and mapped the human c-abl gene, the complete homologue of the viral v-abl gene. They found it contains seven intervening sequences and is not associated with transforming activity in cultured cells.

    Area of Science:

    • Molecular Biology
    • Genetics
    • Oncology

    Background:

    • The viral abl (v-abl) oncogene is derived from the cellular abl (c-abl) gene.
    • Understanding the structure and organization of the human c-abl locus is crucial for cancer research.

    Purpose of the Study:

    • To isolate and characterize the human c-abl gene locus.
    • To investigate the relationship between the human c-abl gene and viral v-abl sequences.
    • To assess the transforming potential of human DNA containing v-abl homologous sequences.

    Main Methods:

    • Isolation of a 64 kb contiguous human DNA region from lung carcinoma DNA using cosmid cloning.
    • Mapping of v-abl homologous sequences within the isolated DNA.
    • Identification and molecular cloning of additional human DNA sequences homologous to portions of v-abl.

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  • Transfection of cosmid DNAs into rat embryo fibroblasts to test for transforming activity.

    • Main Results:

    • A single human c-abl locus, 32 kb in length, was identified and mapped.
    • The human c-abl locus is colinear with the viral v-abl gene and contains at least seven intervening sequences.
    • Eight repetitive DNA regions were found near c-abl coding sequences.
    • Three additional human DNA regions homologous to parts of v-abl were identified, distinct from the primary c-abl locus.
    • Cosmid DNAs with v-abl homologous sequences showed no transforming activity in rat embryo fibroblasts.

    Conclusions:

    • The human c-abl gene locus has been identified and mapped, representing the complete homologue of the viral v-abl gene.
    • The human c-abl locus is structurally organized with multiple intervening sequences and is not oncogenic.
    • Additional human DNA sequences homologous to subgenomic regions of v-abl exist and are distinct from the primary c-abl locus.