Absence of BRAF and NRAS mutations in uveal melanoma

Frank Cruz, Brian P. Rubin, David Wilson, Ajia Town, Arin Schroeder, Andrea Haley, Troy Bainbridge, Michael Heinrich, Christopher Corless

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Uveal melanoma (UM) and cutaneous melanoma (CM) differ significantly in their epidemiological, clinical, immunophenotypical, and cytogenetic features, but the molecular basis for these differences has not been delineated. CMs frequently harbor an activating mutation in either NRAS or the RAS-regulated kinase BRAF, suggesting that either of these oncogenes may increase signaling through the mitogen-activated protein (MAP) kinase pathway and promote melanoma development. The aim of this study was to examine BRAF and NRAS gene mutations in UM. Genomic DNA from CM and UM was screened for mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2 using a combination of denaturing high-performance liquid chromatography and direct sequencing. Mutations in BRAF exon 15 were detected in 16 (36.4%) of 44 CMs and 0 (0%) of 62 UMs. The most common mutation in CM was V599E, but a novel point mutation (L596Q) was identified in two cases and an in-frame deletion/insertion (VKSRWK599-604D) was discovered in one case. No BRAF exon 11 mutations were observed among seven CMs and nine UMs that were wild-type for exon 15. Mutation of NRAS exon 2 was rare in CM [1 (3.7%) of 27] and absent in UM [0 (0%) of 47]. No NRAS exon 1 mutations were detected in either type of melanoma. We conclude that UMs arise independent of oncogenic BRAF and NRAS mutations, an observation that may have implications for therapies targeted to the NRAS-BRAF pathway.

Original languageEnglish (US)
Pages (from-to)5761-5766
Number of pages6
JournalCancer Research
Volume63
Issue number18
StatePublished - Sep 15 2003

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Exons
Mutation
Melanoma
Skin
Proto-Oncogene Proteins B-raf
Uveal melanoma
Mitogen-Activated Protein Kinases
Oncogenes
Point Mutation
Cytogenetics
High Pressure Liquid Chromatography
Observation
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cruz, F., Rubin, B. P., Wilson, D., Town, A., Schroeder, A., Haley, A., ... Corless, C. (2003). Absence of BRAF and NRAS mutations in uveal melanoma. Cancer Research, 63(18), 5761-5766.

Absence of BRAF and NRAS mutations in uveal melanoma. / Cruz, Frank; Rubin, Brian P.; Wilson, David; Town, Ajia; Schroeder, Arin; Haley, Andrea; Bainbridge, Troy; Heinrich, Michael; Corless, Christopher.

In: Cancer Research, Vol. 63, No. 18, 15.09.2003, p. 5761-5766.

Research output: Contribution to journalArticle

Cruz, F, Rubin, BP, Wilson, D, Town, A, Schroeder, A, Haley, A, Bainbridge, T, Heinrich, M & Corless, C 2003, 'Absence of BRAF and NRAS mutations in uveal melanoma', Cancer Research, vol. 63, no. 18, pp. 5761-5766.
Cruz F, Rubin BP, Wilson D, Town A, Schroeder A, Haley A et al. Absence of BRAF and NRAS mutations in uveal melanoma. Cancer Research. 2003 Sep 15;63(18):5761-5766.
Cruz, Frank ; Rubin, Brian P. ; Wilson, David ; Town, Ajia ; Schroeder, Arin ; Haley, Andrea ; Bainbridge, Troy ; Heinrich, Michael ; Corless, Christopher. / Absence of BRAF and NRAS mutations in uveal melanoma. In: Cancer Research. 2003 ; Vol. 63, No. 18. pp. 5761-5766.
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abstract = "Uveal melanoma (UM) and cutaneous melanoma (CM) differ significantly in their epidemiological, clinical, immunophenotypical, and cytogenetic features, but the molecular basis for these differences has not been delineated. CMs frequently harbor an activating mutation in either NRAS or the RAS-regulated kinase BRAF, suggesting that either of these oncogenes may increase signaling through the mitogen-activated protein (MAP) kinase pathway and promote melanoma development. The aim of this study was to examine BRAF and NRAS gene mutations in UM. Genomic DNA from CM and UM was screened for mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2 using a combination of denaturing high-performance liquid chromatography and direct sequencing. Mutations in BRAF exon 15 were detected in 16 (36.4{\%}) of 44 CMs and 0 (0{\%}) of 62 UMs. The most common mutation in CM was V599E, but a novel point mutation (L596Q) was identified in two cases and an in-frame deletion/insertion (VKSRWK599-604D) was discovered in one case. No BRAF exon 11 mutations were observed among seven CMs and nine UMs that were wild-type for exon 15. Mutation of NRAS exon 2 was rare in CM [1 (3.7{\%}) of 27] and absent in UM [0 (0{\%}) of 47]. No NRAS exon 1 mutations were detected in either type of melanoma. We conclude that UMs arise independent of oncogenic BRAF and NRAS mutations, an observation that may have implications for therapies targeted to the NRAS-BRAF pathway.",
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