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

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Abstract

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
Volume30
Issue number20
DOIs
Publication statusPublished - Jul 10 2012

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Mutation Rate
Melanoma
Neoplasm Metastasis
Mutation
Neoplasms
Lymph Nodes
Brain
Skin
Disease Management
DNA Sequence Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Colombino, M., Capone, M., Lissia, A., Cossu, A., Rubino, C., De Giorgi, V., ... Palmieri, G. (2012). BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. Journal of Clinical Oncology, 30(20), 2522-2529. https://doi.org/10.1200/JCO.2011.41.2452

BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. / Colombino, Maria; Capone, Mariaelena; Lissia, Amelia; Cossu, Antonio; Rubino, Corrado; De Giorgi, Vincenzo; Massi, Daniela; Fonsatti, Ester; Staibano, Stefania; Nappi, Oscar; Pagani, Elena; Casula, Milena; Manca, Antonella; Sini, MariaCristina; Franco, Renato; Botti, Gerardo; Caracò, Corrado; Mozzillo, Nicola; Ascierto, Paolo A.; Palmieri, Giuseppe.

In: Journal of Clinical Oncology, Vol. 30, No. 20, 10.07.2012, p. 2522-2529.

Research output: Contribution to journalArticle

Colombino, M, Capone, M, Lissia, A, Cossu, A, Rubino, C, De Giorgi, V, Massi, D, Fonsatti, E, Staibano, S, Nappi, O, Pagani, E, Casula, M, Manca, A, Sini, M, Franco, R, Botti, G, Caracò, C, Mozzillo, N, Ascierto, PA & Palmieri, G 2012, 'BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma', Journal of Clinical Oncology, vol. 30, no. 20, pp. 2522-2529. https://doi.org/10.1200/JCO.2011.41.2452
Colombino, Maria ; Capone, Mariaelena ; Lissia, Amelia ; Cossu, Antonio ; Rubino, Corrado ; De Giorgi, Vincenzo ; Massi, Daniela ; Fonsatti, Ester ; Staibano, Stefania ; Nappi, Oscar ; Pagani, Elena ; Casula, Milena ; Manca, Antonella ; Sini, MariaCristina ; Franco, Renato ; Botti, Gerardo ; Caracò, Corrado ; Mozzillo, Nicola ; Ascierto, Paolo A. ; Palmieri, Giuseppe. / BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 20. pp. 2522-2529.
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abstract = "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.",
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T1 - BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma

AU - Colombino, Maria

AU - Capone, Mariaelena

AU - Lissia, Amelia

AU - Cossu, Antonio

AU - Rubino, Corrado

AU - De Giorgi, Vincenzo

AU - Massi, Daniela

AU - Fonsatti, Ester

AU - Staibano, Stefania

AU - Nappi, Oscar

AU - Pagani, Elena

AU - Casula, Milena

AU - Manca, Antonella

AU - Sini, MariaCristina

AU - Franco, Renato

AU - Botti, Gerardo

AU - Caracò, Corrado

AU - Mozzillo, Nicola

AU - Ascierto, Paolo A.

AU - Palmieri, Giuseppe

PY - 2012/7/10

Y1 - 2012/7/10

N2 - 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.

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