| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 149, 883-893, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
A van Elsas, SF Zerp, S van der Flier, KM Kruse, C Aarnoudse, NK Hayward, DJ Ruiter and PI Schrier
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.
Intermittent or recreational exposure to sunlight is thought to contribute to development of human cutaneous melanoma. We investigated the incidence of ras oncogene mutation in human cutaneous melanoma in connection to sun-exposed body sites in the patient, using a large series of DNA samples derived from paraffin-embedded material as well as from fresh tumor samples and cell lines. We first show that, of the ras family, predominantly N-ras is activated (15%), whereas rarely H- ras or K-ras are mutated. The occurrence of N-ras mutations correlates with continuous exposure to sunlight of the primary tumor site. Of all tumors initiated on chronically sun-exposed body sites, 26% contained mutated N-ras, in contrast to 0% of sun-protected melanomas. Melanoma lesions obtained from patients from North or Central Europe contained fewer N-ras mutations (12%) as compared with patients from Australia (24%). Mutations were specifically associated with nodular melanoma and to a lesser extent with lentigo malignant melanoma. N-ras mutations did not correlate with metastasis or survival parameters. This study identifies a subset of cutaneous melanomas that contain in the primary lesion ultraviolet-induced N-ras mutations, which are maintained through further progression.
This article has been cited by other articles:
 |
|
 |
|
  A. Besaratinia, S.-i. Kim, and G. P. Pfeifer Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells FASEB J, July 1, 2008; 22(7): 2379 - 2392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Maat, S. H. W. Beiboer, M. J. Jager, G. P. M. Luyten, N. A. Gruis, and P. A. van der Velden Epigenetic Regulation Identifies RASEF as a Tumor-Suppressor Gene in Uveal Melanoma Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1291 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. E. Thomas, S. N. Edmiston, A. Alexander, R. C. Millikan, P. A. Groben, H. Hao, D. Tolbert, M. Berwick, K. Busam, C. B. Begg, et al. Number of Nevi and Early-Life Ambient UV Exposure Are Associated with BRAF-Mutant Melanoma Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 991 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Chin, L. A. Garraway, and D. E. Fisher Malignant melanoma: genetics and therapeutics in the genomic era. Genes & Dev., August 15, 2006; 20(16): 2149 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Zhuang, C S Lee, R A Scolyer, S W McCarthy, A A Palmer, X D Zhang, J F Thompson, L P Bron, and P Hersey Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma J. Clin. Pathol., November 1, 2005; 58(11): 1163 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C W Wong, Y S Fan, T L Chan, A S W Chan, L C Ho, T K F Ma, the Cancer Genome Project, S T Yuen, and S Y Leung BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs J. Clin. Pathol., June 1, 2005; 58(6): 640 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cohen, E. Rosenbaum, S. Begum, D. Goldenberg, C. Esche, O. Lavie, D. Sidransky, and W. H. Westra Exon 15 BRAF Mutations Are Uncommon in Melanomas Arising in Nonsun-Exposed Sites Clin. Cancer Res., May 15, 2004; 10(10): 3444 - 3447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wellbrock, L. Ogilvie, D. Hedley, M. Karasarides, J. Martin, D. Niculescu-Duvaz, C. J. Springer, and R. Marais V599EB-RAF is an Oncogene in Melanocytes Cancer Res., April 1, 2004; 64(7): 2338 - 2342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bedogni, M. S. O'Neill, S. M. Welford, D. M. Bouley, A. J. Giaccia, N. C. Denko, and M. B. Powell Topical Treatment with Inhibitors of the Phosphatidylinositol 3'-Kinase/Akt and Raf/Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Pathways Reduces Melanoma Development in Severe Combined Immunodeficient Mice Cancer Res., April 1, 2004; 64(7): 2552 - 2560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Omholt, A. Platz, L. Kanter, U. Ringborg, and J. Hansson NRAS and BRAF Mutations Arise Early during Melanoma Pathogenesis and Are Preserved throughout Tumor Progression Clin. Cancer Res., December 15, 2003; 9(17): 6483 - 6488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Eskandarpour, J. Hashemi, L. Kanter, U. Ringborg, A. Platz, and J. Hansson Frequency of UV-Inducible NRAS Mutations in Melanomas of Patients With Germline CDKN2A Mutations J Natl Cancer Inst, June 4, 2003; 95(11): 790 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Papp, H Pemsel, I Rollwitz, H Schipper, D G Weiss, D Schiffmann, and R Zimmermann Mutational analysis of N-ras, p53, CDKN2A (p16INK4a), p14ARF, CDK4, and MC1R genes in human dysplastic melanocytic naevi J. Med. Genet., February 1, 2003; 40(2): e14 - 14. [Full Text] [PDF]
|
|
|
|
|
|
K. Omholt, S. Karsberg, A. Platz, L. Kanter, U. Ringborg, and J. Hansson Screening of N-ras Codon 61 Mutations in Paired Primary and Metastatic Cutaneous Melanomas: Mutations Occur Early and Persist throughout Tumor Progression Clin. Cancer Res., November 1, 2002; 8(11): 3468 - 3474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Stewart, X. Xu, S. D. Thomas, and D. M. Miller Acridine-modified, clamp-forming antisense oligonucleotides synergize with cisplatin to inhibit c-Myc expression and B16-F0 tumor progression Nucleic Acids Res., June 1, 2002; 30(11): 2565 - 2574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsao Genetics of Nonmelanoma Skin Cancer Arch Dermatol, November 1, 2001; 137(11): 1486 - 1492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Bastian, P. E. LeBoit, and D. Pinkel Mutations and Copy Number Increase of HRAS in Spitz Nevi with Distinctive Histopathological Features Am. J. Pathol., September 1, 2000; 157(3): 967 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tsao, X. Zhang, K. Fowlkes, and F. G. Haluska Relative Reciprocity of NRAS and PTEN/MMAC1 Alterations in Cutaneous Melanoma Cell Lines Cancer Res., April 1, 2000; 60(7): 1800 - 1804. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. Jansen, H. Schlagbauer-Wadl, H. Kahr, E. Heere-Ress, B. X. Mayer, H.-G. Eichler, H. Pehamberger, M. Gana-Weisz, E. Ben-David, Y. Kloog, et al. Novel Ras antagonist blocks human melanoma growth PNAS, November 23, 1999; 96(24): 14019 - 14024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Powell, P. R. Gause, P. Hyman, J. Gregus, M. Lluria-Prevatt, R. Nagle, and G. T. Bowden Induction of melanoma in TPras transgenic mice Carcinogenesis, September 1, 1999; 20(9): 1747 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Papp, H. Pemsel, R. Zimmermann, R. Bastrop, D. G Weiss, and D. Schiffmann Mutational analysis of the N-ras, p53, p16INK4a, CDK4, and MC1R genes in human congenital melanocytic naevi J. Med. Genet., August 1, 1999; 36(8): 610 - 614. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
