Cancer Res  1993 Apr 1;53(7):1625-9 

High mutation frequency in ras genes of skin tumors isolated from DNA repair
deficient xeroderma pigmentosum patients.

Daya-Grosjean L, Robert C, Drougard C, Suarez H, Sarasin A.

Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le
Cancer, Villejuif, France.

Xeroderma pigmentosum (XP) patients are clinically characterized by a very high
incidence of skin cancers on exposed skin, at an early age. XP cells in vitro
are strongly deficient in excision-repair and highly mutagenized by UV light. We
were, therefore, interested in measuring mutation frequency and in determining
mutation spectra in patients' tumors exposed to UV lesions. We chose to look at
oncogene activation in skin tumors with the idea that more mutations,
particularly of the ras gene family, would be found in XP tumors where lesions
remain unrepaired compared to normal individuals. Our results clearly show that
more than a 2-fold significantly higher mutation frequency (50%) of the ras
genes was found in XP in contrast to control tumors (22%). The majority of the
mutations were found at codon 12 of all three ras genes with a preponderance for
N-ras in XP samples. The mutation spectra indicate that all mutations found were
located opposite pyrimidine-pyrimidine sequences which represent a hot spot for
UV-induced DNA lesions. Most of the mutations were of the type expected from
studies performed in vitro with model systems. This high mutation frequency in
XP was accompanied by a very high level of Ha-ras and c-myc gene amplification
and rearrangement. All these data are consistent with a fundamental role of
unrepaired UV-induced DNA lesions as an initiating event in human skin tumors on
exposed parts of the body.

PMID: 8453633 [PubMed - indexed for MEDLINE]