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Establishment and Characterization of a Melanoma Cell Line from a Xeroderma Pigmentosum Patient: Activation of N-ras at a Potential Pyrimidine Dimer Site¹

Department of Cell Biology and Genetics, Erasmus University, P. O. Box 1738, 3000 DR Rotterdam; [W. K., M. P. M., J. C. M. L., E. M. E. S., D. B., J. H. J. H.]; and the Department of Medical Biochemistry, Sylvius Laboratories, State University Leiden, Leiden, The Netherlands [J. L. B.]

Patients suffering from the genetic disorder xeroderma pigmentosum (XP) display an extreme sensitivity of their skin to sun (UV) exposure and predisposition to skin cancer due to deficiencies in the excision DNA repair pathway. Here we describe the establishment and characterization of the first tumor cell line derived from an XP patient (belonging to complementation group C). The melanoma cell line designated XP44RO(Mel) has retained its tumorigenic and XP phenotype (UV sensitivity, reduced unscheduled DNA synthesis) and showed karyotypic abnormalities characteristic of melanomas. Transfection of XP44RO(Mel) DNA to NIH3T3 cells and oligonucleotide hybridization revealed that the N-ras oncogene was activated by an A·T to T·A or C·G transversion at the third position of codon 61. This mutation occurs at a dipyrimidine site. It is likely initiated by a UV-induced pyrimidine dimer and is of a type rarely observed in mammalian shuttle vector systems and endogenous genes after UV irradiation.

¹ This work was financially supported by EURATOM (contract B16-141-NL) and MEDIGON, Foundation of Medical Scientific for Research in the Netherlands.

² To whom requests for reprints should be addressed, at Department of Cell Biology and Genetics, Erasmus University, P. O. Box 1738, 3000 DR Rotterdam, The Netherlands.

Received 6/14/88. Revised 11/ 2/88. Accepted 11/ 8/88.

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