Abstract
Molecular analysis of p53 and patched (PTCH), two candidate tumor suppressor genes for non-melanocytic skin cancer, was performed in skin tumors from six patients affected by the cancer-prone disease xeroderma pigmentosum (XP). UV-specific p53 mutations were detected at a frequency of 38–50% in all the tumor types analysed, including melanomas. Additional analysis of PTCH mutations in the subset of eight basal call carcinomas (BCC) revealed a very high mutation frequency of this gene (90%) which exceeded that detected in the p53 gene in the same tumors (38%). PTCH mutations were predominantly UV-specific C>T transitions. This mutation pattern is different from that reported in BCC from normal donors where PTCH mutation frequency is 27% and mutations are frequently deletions and insertions. These findings suggest that PTCH mutations represent an earlier event in BCC development than p53 alterations and that the inability of XP patients to repair UV-induced PTCH mutations might significantly contribute to the early and frequent appearance of BCC observed in these patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aszterbaum M, Rothman A, Johnson RL, Fisher M, Xie J, Bonifas JM, Zhang X, Scott MP and Epstein EHJ. . 1998 J. Invest. Dermatol. 110: 885–888.
Bodak N, Queille S, Avril MF, Bouadjar B, Drougard C, Sarasin A and Daya-Grosjean L. . 1999 Proc. Natl. Acad. Sci. USA 96: 5117–5122.
Chidambaram A, Goldstein AM, Gailani MR, Gerrard B, Bale SJ, DiGiovanna JJ, Bale AE and Dean M. . 1996 Cancer Res. 56: 4599–4601.
Cordonnier AM, Lehmann AR and Fuchs RP. . 1999 Mol. Cell. Biol. 19: 2206–2211.
D'Errico M, Calcagnile AS, Corona R, Fucci M, Annessi G, Baliva G, Tosti ME, Pasquini P and Dogliotti E. . 1997 Cancer Res. 57: 747–752.
Dahmane N, Lee J, Robins P, Heller P and Ruiz i Altaba A. . 1997 Nature 389: 876–881.
de Laat WL, Jaspers NGJ and Hoeijmakers JHJ. . 1999 Genes and Development 13: 768–785.
Dogliotti E, Hainaut P, Hernandez T, D'Errico M and DeMarini DM. . 1998 Genes and Environment in Cancer, vol. 154, Recent results in Cancer Research, Schwab et al. (eds). Berlin-Heidelberg: Springer-Verlag pp. 97–124.
Dumaz N, Drougard A, Sarasin A and Daya-Grosjean L. . 1993 Proc. Natl. Acad. Sci. USA 90: 10529–10533.
Eklund LK, Lindstrom E, Unden AB, Lundh-Rozell B, Stahle-Backdahl M, Zaphiropoulos PG, Toftgard R and Soderkvist P. . 1998 Mol. Carcinogenesis 21: 87–92.
Gailani MR and Bale AE. . 1997 J. Natl. Cancer Inst. 89: 1103–1109.
Gailani MR, Stahle-Backdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Unden AB, Dean M, Brash DE, Bale AE and Toftgard R. . 1996 Nature Genetics 14: 78–81.
Giglia G, Dumaz N, Drougard C, Avril M-F, Daya-Grosjean L and Sarasin A. . 1998 Proc. Natl. Acad. Sci. USA 58: 4402–4409.
Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B and Bale AE. . 1996 Cell 85: 841–851.
Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH and Scott MP. . 1996 Science 272: 1668–1671.
Lubbe J, Reichel M, Burg G and Kleihues P. . 1994 J. Inv. Dermatol. 102: 819–821.
Masutani C, Kusomoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K and Hanaoka F. . 1999 Nature 399: 700–704.
McGregor WG, Wel D, Maher VM and McCormick JJ. . 1999 Mol. Cell. Biol. 19: 147–154.
Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein EH and Scott MP. . 1997 Science 276: 817–821.
Papp T, Jafari M and Schiffmann D. . 1996 J. Cancer Res. & Clin. Oncol. 122: 541–548.
Rapic-Otrin V, Kuraoka I, Nardo T, McLenigan M, Eker APM, Stefanini M, Levine AS and Wood RD. . 1998 Mol. Cell. Biol. 18: 3182–3190.
Stefanini M, Lagomarsini P, Giliani S, Nardo T, Botta E, Peserico A, Kleijer WJ, Lehmann AR and Sarasin A. . 1993 Carcinogenesis 14: 1101–1105.
Tornaletti S and Pfeifer GP. . 1994 Science 263: 1436–1438.
Unden AB, Holmberg E, Lundh-Rozell B, Stahle-Backdahl M, Zaphiropoulos PG, Toftgard R and Vorechovsky I. . 1996 Cancer Res. 56: 4562–4565.
Wang Y-C, Maher VM, Mitchell DL and McCormick JJ. . 1993 Mol. Cell. Biol. 13: 4276–4283.
Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B and Chenevix-Trench G. . 1997 Am. J. Hum. Genet. 60: 21–26.
Wolter M, Reifenberger J, Sommer C, Ruzicka T and Reifenberger G. . 1997 Cancer Res. 57: 2581–2585.
Xie J, Murone M, Luoh S-M, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam C-W, Hynes M, Goddard A, Rosenthal A, Epstein Jr EH and deSauvage FJ. . 1998 Nature 391: 90–92.
Acknowledgements
This work was supported in part by AIRC grant to M Stefanini.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
D'Errico, M., Calcagnile, A., Canzona, F. et al. UV mutation signature in tumor suppressor genes involved in skin carcinogenesis in xeroderma pigmentosum patients. Oncogene 19, 463–467 (2000). https://doi.org/10.1038/sj.onc.1203313
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203313
Keywords
This article is cited by
-
UV Fingerprints Predominate in the PTCH Mutation Spectra of Basal Cell Carcinomas Independent of Clinical Phenotype
Journal of Investigative Dermatology (2007)
-
Basalzellkarzinom
Der Hautarzt (2007)
-
PATCHED and p53 gene alterations in sporadic and hereditary basal cell cancer
Oncogene (2001)
