A primary melanoma and its asynchronous metastasis highlight the role of BRAF, CDKN2A, and TERT. (11th December 2014)

• Record Type: Journal Article
• Authors: Hosler, Gregory A.; Davoli, Teresa; Mender, Ilgen; Litzner, Brandon; Choi, Jaehyuk; Kapur, Payal; Shay, Jerry W.; Wang, Richard C.
• Is Part Of: Journal of cutaneous pathology. Volume 42:Number 2(2015:Feb.)
• Page Start: 108
• Page End: 117
• Publication Date: 2014-12-11
• Subjects: Skin -- Diseases -- Periodicals; Dermatology -- Periodicals; 616
• DOI: 10.1111/cup.12444
• Languages: English
• ISSNs: 0303-6987

Abstract

<abstract abstract-type="main" id="cup12444-abs-0001"> <title>Abstract</title> <sec id="cup12444-sec-0001" sec-type="section"> <title>Background</title> <p id="cup12444-para-0001">Alterations in pathways including <italic>BRAF</italic>, <italic>CDKN2A</italic>, and <italic>TERT</italic> contribute to the development of melanoma, but the sequence in which the genetic alterations occur and their prognostic significance remains unclear. To clarify the role of these pathways, we analyzed a primary melanoma and its metastasis.</p> </sec> <sec id="cup12444-sec-0002" sec-type="section"> <title>Methods</title> <p id="cup12444-para-0002">Immunohistochemistry for BRAF‐V600E, Sanger sequencing of <italic>BRAF</italic> and the <italic>TERT</italic> promoter, fluorescence <italic>in‐situ</italic> hybridization, and telomere analyses were performed on a primary melanoma and its asynchronous cerebellar metastasis. Using the log‐rank test and Cox‐proportional model, the cancer genome atlas (TCGA) cohort of melanomas was analyzed for the effect of <italic>BRAF</italic> mutation and <italic>CDKN2A</italic> loss on survival.</p> </sec> <sec id="cup12444-sec-0003" sec-type="section"> <title>Results</title> <p id="cup12444-para-0003">The primary melanoma expressed mutant <italic>BRAF</italic>‐V600E and possessed a homozygous deletion of <italic>CDKN2A</italic>. In addition to these early defects, the metastatic lesion also possessed evidence of aneuploidy and an activating mutation of the <italic>TERT</italic> promoter. In the TCGA melanoma cohort, there was a non‐significant trend toward poor prognosis in early stage cutaneous melanoma patients with concomitant <italic>BRAF</italic> mutation and <italic>CDKN2A</italic> loss.</p> </sec> <sec id="cup12444-sec-0004" sec-type="section"> <title>Conclusion</title> <p id="cup12444-para-0004"> <italic>BRAF</italic> mutation and <italic>CDKN2A</italic> loss occurred early and <italic>TERT</italic> promoter mutation later in a case of lethal metastatic melanoma. The effects of these pathways on survival warrant further investigation in early stage cutaneous melanoma patients.</p> </sec> </abstract>