BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma

Maria Colombino, Mariaelena Capone, Amelia Lissia, Antonio Cossu, Corrado Rubino, Vincenzo De Giorgi, Daniela Massi, Ester Fonsatti, Stefania Staibano, Oscar Nappi, Elena Pagani, Milena Casula, Antonella Manca, MariaCristina Sini, Renato Franco, Gerardo Botti, Corrado Caracò, Nicola Mozzillo, Paolo A. Ascierto, Giuseppe Palmieri

Research output: Contribution to journalArticlepeer-review


Purpose: The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues. Patients and Methods: In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. Results: BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples. Conclusion: In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.

Original languageEnglish
Pages (from-to)2522-2529
Number of pages8
JournalJournal of Clinical Oncology
Issue number20
Publication statusPublished - Jul 10 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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