Establishment and characterization of a melanoma cell line from a xeroderma pigmentosum patient: activation of N-ras at a potential pyrimidine dimer site.
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.
Keijzer
W
W
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Mulder
M P
MP
Langeveld
J C
JC
Smit
E M
EM
Bos
J L
JL
Bootsma
D
D
Hoeijmakers
J H
JH
D000818:Animals; D002648:Child; D002869:Chromosome Aberrations; D004260:DNA Repair; D011905:Genes, ras; D006801:Humans; D008545:Melanoma / Q000209:etiology / Q000473:pathology*; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011740:Pyrimidine Dimers / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000235:genetics*
D011740:Pyrimidine Dimers