Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2011 Jan 15;17(2):229-35. doi: 10.1158/1078-0432.CCR-10-2276. Epub 2010 Oct 25.

Clinical correlates of NRAS and BRAF mutations in primary human melanoma.

Author information

  • 1Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. jaellerh@mdanderson.org

Erratum in

  • Clin Cancer Res. 2011 Mar 15;17(6):1641.

Abstract

PURPOSE:

NRAS and BRAF mutations are common in cutaneous melanomas, although rarely detected mutually in the same tumor. Distinct clinical correlates of these mutations have not been described, despite in vitro data suggesting enhanced oncogenic effects. This study was designed to test the hypothesis that primary human cutaneous melanomas harboring mutations in NRAS or BRAF display a more aggressive clinical phenotype than tumors wild type at both loci.

EXPERIMENTAL DESIGN:

Microdissection of 223 primary melanomas was carried out, followed by determination of the NRAS and BRAF mutational status. Genotypic findings were correlated with features known to influence tumor behavior including age, gender, Breslow depth, Clark level, mitotic rate, the presence of ulceration, and American Joint Committee on Cancer (AJCC) staging.

RESULTS:

Breslow depth and Clark level varied significantly among the genotypes, with NRAS mutants showing the deepest levels and wild-type tumors the least depth. Ulceration also differed significantly among the genotypes, with BRAF mutants demonstrating the highest rate. In addition, tumors with mutated NRAS were more likely to be located on the extremities. Patients whose tumors carried either mutation presented with more advanced AJCC stages compared with patients with wild-type tumors, and specifically, were more likely to have stage III disease at diagnosis. Overall survival did not differ among the 3 groups.

CONCLUSIONS:

Distinct clinical phenotypes exist for melanomas bearing NRAS and BRAF mutations, whether considered together or separately, and are associated with features known to predict aggressive tumor behavior. The impact of these mutations is most evident at earlier stages of disease progression.

©2010 AACR.

PMID:
20975100
[PubMed - indexed for MEDLINE]
PMCID:
PMC3022950
Free PMC Article

Images from this publication.See all images (2)Free text

Figure 1
Figure 2
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk