Lack of BRAF mutation in primary uveal melanoma.

PURPOSE BRAF T1796A activating mutations have been found in a high proportion of cutaneous melanomas, cutaneous nevi, and papillary thyroid carcinoma and in a small fraction of other cancers. This study was designed to investigate the incidence of BRAF T1796A mutation in uveal melanoma. METHODS Twenty-nine formalin-fixed, paraffin-embedded posterior uveal melanomas were included in the study. DNA was extracted from the paraffin sections followed by PCR amplification of exon 15 and detection of the common BRAF missense mutation (T-->A transversion at nucleotide 1796) using restriction enzyme analysis. RESULTS Although positive cutaneous melanoma control cell lines harbored the T1796A BRAF mutation, none of the 29 uveal melanomas harbored the mutation. CONCLUSIONS These data suggest that BRAF T1796A activating mutation is not common in primary uveal melanoma. These findings are in accord with known differences in tumorigenesis between uveal and cutaneous melanomas.

[1]  P. Ladenson,et al.  BRAF mutation in papillary thyroid carcinoma. , 2003, Journal of the National Cancer Institute.

[2]  N. Weiss,et al.  Relationship of uveal and cutaneous malignant melanoma in persons with multiple primary tumors , 2002, International journal of cancer.

[3]  D. Kelsell,et al.  Mutational analysis of selected genes in the TGFbeta, Wnt, pRb, and p53 pathways in primary uveal melanoma. , 2002, Investigative ophthalmology & visual science.

[4]  K. Kinzler,et al.  Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status , 2002, Nature.

[5]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[6]  R. E. Kalina,et al.  Immunophenotypic differences between uveal and cutaneous melanomas. , 2002, Archives of ophthalmology.

[7]  P. Maloney,et al.  Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the retinoblastoma locus, in uveal melanoma. , 2001, Investigative ophthalmology & visual science.

[8]  J. Keunen,et al.  Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients. , 2001, Investigative ophthalmology & visual science.

[9]  P. Guénel,et al.  Occupational risk factors, ultraviolet radiation, and ocular melanoma: a case–control study in France , 2001, Cancer Causes & Control.

[10]  L. Desjardins,et al.  Individuals with presumably hereditary uveal melanoma do not harbour germline mutations in the coding regions of either the P16INK4A, P14ARF or cdk4 genes , 2000, British Journal of Cancer.

[11]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[12]  D. Sidransky,et al.  Allelotype of posterior uveal melanoma: implications for a bifurcated tumor progression pathway. , 1999, Cancer research.

[13]  L. Karnell,et al.  The National Cancer Data Base report on cutaneous and noncutaneous melanoma , 1998, Cancer.

[14]  L. Happerfield,et al.  Comparative analysis of integrins in vitro and in vivo in uveal and cutaneous melanomas. , 1998, British Journal of Cancer.

[15]  P. D. de Jong,et al.  Prognostic parameters in uveal melanoma: a review. , 1996, Survey of ophthalmology.

[16]  N. Bornfeld,et al.  Prognostic implications of monosomy 3 in uveal melanoma , 1996, The Lancet.

[17]  J. O'Brien,et al.  Investigation of the role of the ras protooncogene point mutation in human uveal melanomas. , 1993, Investigative ophthalmology & visual science.

[18]  N. Bornfeld,et al.  Loss of chromosome 3 alleles and multiplication of chromosome 8 alleles in uveal melanoma , 1992, Genes, chromosomes & cancer.

[19]  C. M. Mooy,et al.  No N-ras mutations in human uveal melanoma: the role of ultraviolet light revisited. , 1991, British Journal of Cancer.

[20]  R N Hoover,et al.  Sunlight exposure as risk factor for intraocular malignant melanoma. , 1985, The New England journal of medicine.

[21]  J. Birdsell,et al.  Risk factors for ocular melanoma: Western Canada Melanoma Study. , 1985, Journal of the National Cancer Institute.

[22]  R. Gallagher,et al.  Color as a risk factor in iris melanoma. , 1984, American journal of ophthalmology.

[23]  E. Elias,et al.  Biologic behavior of ocular malignant melanoma and comparison with melanoma of the head and neck. , 1980, American journal of surgery.

[24]  P. Meltzer,et al.  High frequency of BRAF mutations in nevi , 2003, Nature Genetics.

[25]  X. F. Zhang,et al.  Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. , 2001, Recent progress in hormone research.