Clinical characteristics and outcomes with specific BRAF and NRAS mutations in patients with metastatic melanoma. Issue 21 (6th August 2013)

• Record Type: Journal Article
• Authors: Bucheit, Amanda D.; Syklawer, Erica; Jakob, John A.; Bassett, Roland L.; Curry, Jonathan L.; Gershenwald, Jeffrey E.; Kim, Kevin B.; Hwu, Patrick; Lazar, Alexander J.; Davies, Michael A.
• Is Part Of: Cancer. Volume 119:Issue 21(2013)
• Page Start: 3821
• Page End: 3829
• Publication Date: 2013-08-06
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28306
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28306-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Hotspot mutations in <italic>BRAF</italic> and <italic>NRAS</italic> are the most common somatic events in patients with melanoma. These mutations occur at highly conserved residues, but include several different substitutions. To determine whether specific mutations are clinically important to differentiate, tumor characteristics and clinical outcomes were compared among patients with advanced melanoma with 1) <italic>BRAF V600E</italic> versus <italic>V600K</italic> mutations and 2) <italic>NRAS</italic> exon 1 versus exon 2 mutations.</p> </sec> <sec id="cncr28306-sec-0002" sec-type="section"> <title>METHODS</title> <p>Retrospective clinical and pathologic data were collected for patients with advanced melanoma with <italic>BRAF</italic> or <italic>NRAS</italic> mutations. The demographics, tumor characteristics, and clinical outcomes of the patients were compared to identify significant mutation‐specific associations.</p> </sec> <sec id="cncr28306-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Among 302 patients with activating <italic>BRAF</italic> mutations, 76% had <italic>BRAF V600E</italic> and 24% had <italic>V600K</italic> substitutions. Compared with <italic>V600E</italic>, the presence of a <italic>V600K</italic> mutation was significantly associated with older age (median, 60.0 years vs 44.7 years; <italic>P</italic> < .001), male sex (80% vs 59%; <italic>P</italic> = .001), head/neck primary tumor location (30% vs 15%; <italic>P</italic> = .0026), shorter interval to stage IV disease (0.98 years vs 2.8 years; <italic>P</italic> = .015), and a shorter overall survival from the time of diagnosis of stage IV disease (median, 2.44 years vs 1.25 years; hazards ratio, 1.68 [<italic>P</italic> = .014]). Comparison of 136 patients with <italic>NRAS</italic> exon 1 (18%) and exon 2 (82%) mutations found an association with primary tumor histology (<italic>P</italic> = .0096) only.</p> </sec> <sec id="cncr28306-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>The presence of different substitutions at <italic>BRAF V600</italic> correlates with patient demographics, tumor characteristics, and prognosis. These findings demonstrate the presence of mutation‐specific clinical differences between different <italic>BRAF</italic> genotypes in patients with melanoma, and support the incorporation of this information in patient evaluation and clinical trial design. Cancer 2013;119:3821–3829. © 2013 American Cancer Society.</p> </sec> </abstract>