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Rearrangement of the Human mel Gene, the rab 8 Homologue, in Human Malignant Melanomas

  • Rose Ann Padua
  • David Hughes
  • Elaine Nimmo
  • Peter Schrier
  • Keith Johnson
Part of the NATO ASI Series book series (NSSA, volume 220)

Abstract

The human MEL gene was originally isolated following transfection into NIH3T3 mouse fibroblast cells of DNA from a human melanoma cell line NKI4. MEL was mapped to chromosome 19 (pl3.2), a region in which a number of translocation breakpoints occur. We have sequenced MEL cDNA clones and shown significant homology to the RAS-related YPT1 proteins and more specifically, identity with the recently described canine RAB 8. The original transfectant from which MEL was isolated appeared to comprise of complex rearrangements involving human sequences mapping on chromosome 8. Furthermore, most of the MEL sequences, apart from the putative first extron, were absent. The presence of the human MEL sequences may be fortuitous in this transfectant and the transforming gene has yet to be isolated. However, 12 melanoma cell lines and 20 fresh melanoma tumours were screened for MEL gene rearrangements and. DNA from a single patient with a tumour metastasis from the intestinal tract was found to have rearranged MEL sequences. DNA from this tumour was positive in NIH3T3 focus formation assays, producing anchorage independent foci with human repetitive sequences present. One of these transformants was tested and found to be tumorigenic in nude mice. These transformants showed no evidence of human H, K or N RAS or MEL activation. Six additional metastases from this patient lacked this rearrangement, suggesting that the gene rearrangement observed may be associated with late events in the evolution of the tumour metastasis.

Keywords

Melanoma Cell Line Transforming Gene Melanoma Tumour Translocation Breakpoint Complex Rearrangement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Rose Ann Padua
    • 1
  • David Hughes
    • 1
  • Elaine Nimmo
    • 2
  • Peter Schrier
    • 3
  • Keith Johnson
    • 2
  1. 1.LRF Preleukaemia UnitUniversity of Wales College of MedicineCardiffUK
  2. 2.Department of AnatomyCharing Cross and Westminster Medical SchoolLondonUK
  3. 3.Laboratorium voor Klinische OncologieLeidenNetherlands

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