Association of CDK4 germline and BRAF somatic mutations in a patient with multiple primary melanomas and BRAF inhibitor resistance. Issue 5 (October 2015)

• Record Type: Journal Article
• Authors: Governa, Maurizio; Caprarella, Evelina; Dalla Pozza, Edoardo; Vigato, Enrico; Maritan, Monia; Caputo, Glenda G.; Zannoni, Marina; Rosina, Paolo; Elefanti, Lisa; Stagni, Camilla; Menin, Chiara
• Is Part Of: Melanoma research. Volume 25:Issue 5(2015)
• Publication Date: 2015-10
• Subjects: Melanoma -- Periodicals; Melanoma -- Periodicals; Melanomen; 616.99477
• DOI: 10.1097/CMR.0000000000000173
• Languages: English
• ISSNs: 0960-8931

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Many genetic alterations, including predisposing or somatic mutations, may contribute toward the development of melanoma. Although <italic>CDKN2A</italic> and <italic>CDK4</italic> are high-penetrance genes for melanoma, <italic>MC1R</italic> is a low-penetrance gene that has been associated most consistently with the disease. Moreover, <italic>BRAF</italic> is the most frequently somatically altered oncogene and is a validated therapeutic target in melanoma. This paper reports a case of multiple primary melanoma with germline <italic>CDK4</italic> mutation, <italic>MC1R</italic> variant, and somatic <italic>BRAF</italic> mutation in nine out of 10 melanomas, indicating that a common pathogenesis, because of a predisposing genetic background, may be shared among distinct subsequent melanomas of probable clonal origin. After 3 months of targeted therapy with <italic>BRAF</italic> inhibitor, our patient developed resistance with rapid progression of the disease leading to death. This is the first case in which early resistance to <italic>BRAF</italic> inhibitor has been reported in a patient with <italic>CDK4</italic> germline mutation.</p> </sec> </abstract>