Determinants of BRAF mutations in primary melanomas

Janet L. Maldonado, Jane Fridlyand, Hetal Patel, Ajay N. Jain, Klaus Busam, Toshiro Kageshita, Tomomichi Ono, Donna Albertson, Dan Pinkel, Boris C. Bastian

Research output: Contribution to journalArticle

Abstract

The RAS/mitogen-activated protein kinase pathway sends external growth-promoting signals to the nucleus. BRAF, a critical serine/threonine kinase in this pathway, is frequently activated by somatic mutation in melanoma. Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test). By contrast, BRAF mutations in melanomas on chronically sun-damaged skin (1 of 12 patients) and melanomas on skin relatively or completely unexposed to sun, such as palms, soles, subungual sites (6 of 39 patients), and mucosal membranes (2 of 21 patients) are rare. We found no association of mutation status with clinical outcome or with the presence of an associated melanocytic nevus. The mutated BRAF allele was frequently found at an elevated copy number, implicating BRAF as one of the factors driving selection for the frequent copy number increases of chromosome 7q in melanoma. In summary, the uneven distribution of BRAF mutations strongly suggests distinct genetic pathways leading to melanoma. The high mutation frequency in melanomas arising on intermittently sun-exposed skin suggests a complex causative role of such exposure that mandates further evaluation.

Original languageEnglish (US)
Pages (from-to)1878-1880
Number of pages3
JournalJournal of the National Cancer Institute
Volume95
Issue number24
StatePublished - Dec 17 2003

Fingerprint

Melanoma
Mutation
Solar System
Skin
Pigmented Nevus
Protein-Serine-Threonine Kinases
Mutation Rate
Mitogen-Activated Protein Kinases
Chromosomes
Alleles
Membranes
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Maldonado, J. L., Fridlyand, J., Patel, H., Jain, A. N., Busam, K., Kageshita, T., ... Bastian, B. C. (2003). Determinants of BRAF mutations in primary melanomas. Journal of the National Cancer Institute, 95(24), 1878-1880.

Determinants of BRAF mutations in primary melanomas. / Maldonado, Janet L.; Fridlyand, Jane; Patel, Hetal; Jain, Ajay N.; Busam, Klaus; Kageshita, Toshiro; Ono, Tomomichi; Albertson, Donna; Pinkel, Dan; Bastian, Boris C.

In: Journal of the National Cancer Institute, Vol. 95, No. 24, 17.12.2003, p. 1878-1880.

Research output: Contribution to journalArticle

Maldonado, JL, Fridlyand, J, Patel, H, Jain, AN, Busam, K, Kageshita, T, Ono, T, Albertson, D, Pinkel, D & Bastian, BC 2003, 'Determinants of BRAF mutations in primary melanomas', Journal of the National Cancer Institute, vol. 95, no. 24, pp. 1878-1880.
Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T et al. Determinants of BRAF mutations in primary melanomas. Journal of the National Cancer Institute. 2003 Dec 17;95(24):1878-1880.
Maldonado, Janet L. ; Fridlyand, Jane ; Patel, Hetal ; Jain, Ajay N. ; Busam, Klaus ; Kageshita, Toshiro ; Ono, Tomomichi ; Albertson, Donna ; Pinkel, Dan ; Bastian, Boris C. / Determinants of BRAF mutations in primary melanomas. In: Journal of the National Cancer Institute. 2003 ; Vol. 95, No. 24. pp. 1878-1880.
@article{2818cbda3b864a76908a9f19d82c2347,
title = "Determinants of BRAF mutations in primary melanomas",
abstract = "The RAS/mitogen-activated protein kinase pathway sends external growth-promoting signals to the nucleus. BRAF, a critical serine/threonine kinase in this pathway, is frequently activated by somatic mutation in melanoma. Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test). By contrast, BRAF mutations in melanomas on chronically sun-damaged skin (1 of 12 patients) and melanomas on skin relatively or completely unexposed to sun, such as palms, soles, subungual sites (6 of 39 patients), and mucosal membranes (2 of 21 patients) are rare. We found no association of mutation status with clinical outcome or with the presence of an associated melanocytic nevus. The mutated BRAF allele was frequently found at an elevated copy number, implicating BRAF as one of the factors driving selection for the frequent copy number increases of chromosome 7q in melanoma. In summary, the uneven distribution of BRAF mutations strongly suggests distinct genetic pathways leading to melanoma. The high mutation frequency in melanomas arising on intermittently sun-exposed skin suggests a complex causative role of such exposure that mandates further evaluation.",
author = "Maldonado, {Janet L.} and Jane Fridlyand and Hetal Patel and Jain, {Ajay N.} and Klaus Busam and Toshiro Kageshita and Tomomichi Ono and Donna Albertson and Dan Pinkel and Bastian, {Boris C.}",
year = "2003",
month = "12",
day = "17",
language = "English (US)",
volume = "95",
pages = "1878--1880",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "24",

}

TY - JOUR

T1 - Determinants of BRAF mutations in primary melanomas

AU - Maldonado, Janet L.

AU - Fridlyand, Jane

AU - Patel, Hetal

AU - Jain, Ajay N.

AU - Busam, Klaus

AU - Kageshita, Toshiro

AU - Ono, Tomomichi

AU - Albertson, Donna

AU - Pinkel, Dan

AU - Bastian, Boris C.

PY - 2003/12/17

Y1 - 2003/12/17

N2 - The RAS/mitogen-activated protein kinase pathway sends external growth-promoting signals to the nucleus. BRAF, a critical serine/threonine kinase in this pathway, is frequently activated by somatic mutation in melanoma. Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test). By contrast, BRAF mutations in melanomas on chronically sun-damaged skin (1 of 12 patients) and melanomas on skin relatively or completely unexposed to sun, such as palms, soles, subungual sites (6 of 39 patients), and mucosal membranes (2 of 21 patients) are rare. We found no association of mutation status with clinical outcome or with the presence of an associated melanocytic nevus. The mutated BRAF allele was frequently found at an elevated copy number, implicating BRAF as one of the factors driving selection for the frequent copy number increases of chromosome 7q in melanoma. In summary, the uneven distribution of BRAF mutations strongly suggests distinct genetic pathways leading to melanoma. The high mutation frequency in melanomas arising on intermittently sun-exposed skin suggests a complex causative role of such exposure that mandates further evaluation.

AB - The RAS/mitogen-activated protein kinase pathway sends external growth-promoting signals to the nucleus. BRAF, a critical serine/threonine kinase in this pathway, is frequently activated by somatic mutation in melanoma. Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test). By contrast, BRAF mutations in melanomas on chronically sun-damaged skin (1 of 12 patients) and melanomas on skin relatively or completely unexposed to sun, such as palms, soles, subungual sites (6 of 39 patients), and mucosal membranes (2 of 21 patients) are rare. We found no association of mutation status with clinical outcome or with the presence of an associated melanocytic nevus. The mutated BRAF allele was frequently found at an elevated copy number, implicating BRAF as one of the factors driving selection for the frequent copy number increases of chromosome 7q in melanoma. In summary, the uneven distribution of BRAF mutations strongly suggests distinct genetic pathways leading to melanoma. The high mutation frequency in melanomas arising on intermittently sun-exposed skin suggests a complex causative role of such exposure that mandates further evaluation.

UR - http://www.scopus.com/inward/record.url?scp=0346728596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346728596&partnerID=8YFLogxK

M3 - Article

VL - 95

SP - 1878

EP - 1880

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 24

ER -