Discrepant alterations in main candidate genes among multiple primary melanomas

Maria Colombino, MariaCristina Sini, Amelia Lissia, Vincenzo De Giorgi, Ignazio Stanganelli, Fabrizio Ayala, Daniela Massi, Corrado Rubino, Antonella Manca, Panagiotis Paliogiannis, Susanna Rossari, Serena Magi, Laura Mazzoni, Gerardo Botti, Mariaelena Capone, Marco Palla, Paolo A. Ascierto, Antonio Cossu, Giuseppe Palmieri, C. CaracòV. Chiarion Sileni, N. Mozzillo, P. Queirolo, C. R. Rossi, A. Testori

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).Methods: One hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N = 229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications. Results: BRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p <0.001) and CyclinD1 (p = 0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors.Conclusions: The low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.

Original languageEnglish
Article number117
JournalJournal of Translational Medicine
Volume12
Issue number1
DOIs
Publication statusPublished - May 8 2014

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Tumors
Melanoma
Genes
Amplification
Tissue
Mutation
Neoplasms
Gene Amplification
Mutation Rate
Regulator Genes

Keywords

  • Gene amplification
  • Melanomagenesis
  • Molecular classification
  • Multiple melanoma
  • Mutation analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Colombino, M., Sini, M., Lissia, A., De Giorgi, V., Stanganelli, I., Ayala, F., ... Testori, A. (2014). Discrepant alterations in main candidate genes among multiple primary melanomas. Journal of Translational Medicine, 12(1), [117]. https://doi.org/10.1186/1479-5876-12-117

Discrepant alterations in main candidate genes among multiple primary melanomas. / Colombino, Maria; Sini, MariaCristina; Lissia, Amelia; De Giorgi, Vincenzo; Stanganelli, Ignazio; Ayala, Fabrizio; Massi, Daniela; Rubino, Corrado; Manca, Antonella; Paliogiannis, Panagiotis; Rossari, Susanna; Magi, Serena; Mazzoni, Laura; Botti, Gerardo; Capone, Mariaelena; Palla, Marco; Ascierto, Paolo A.; Cossu, Antonio; Palmieri, Giuseppe; Caracò, C.; Chiarion Sileni, V.; Mozzillo, N.; Queirolo, P.; Rossi, C. R.; Testori, A.

In: Journal of Translational Medicine, Vol. 12, No. 1, 117, 08.05.2014.

Research output: Contribution to journalArticle

Colombino, M, Sini, M, Lissia, A, De Giorgi, V, Stanganelli, I, Ayala, F, Massi, D, Rubino, C, Manca, A, Paliogiannis, P, Rossari, S, Magi, S, Mazzoni, L, Botti, G, Capone, M, Palla, M, Ascierto, PA, Cossu, A, Palmieri, G, Caracò, C, Chiarion Sileni, V, Mozzillo, N, Queirolo, P, Rossi, CR & Testori, A 2014, 'Discrepant alterations in main candidate genes among multiple primary melanomas', Journal of Translational Medicine, vol. 12, no. 1, 117. https://doi.org/10.1186/1479-5876-12-117
Colombino, Maria ; Sini, MariaCristina ; Lissia, Amelia ; De Giorgi, Vincenzo ; Stanganelli, Ignazio ; Ayala, Fabrizio ; Massi, Daniela ; Rubino, Corrado ; Manca, Antonella ; Paliogiannis, Panagiotis ; Rossari, Susanna ; Magi, Serena ; Mazzoni, Laura ; Botti, Gerardo ; Capone, Mariaelena ; Palla, Marco ; Ascierto, Paolo A. ; Cossu, Antonio ; Palmieri, Giuseppe ; Caracò, C. ; Chiarion Sileni, V. ; Mozzillo, N. ; Queirolo, P. ; Rossi, C. R. ; Testori, A. / Discrepant alterations in main candidate genes among multiple primary melanomas. In: Journal of Translational Medicine. 2014 ; Vol. 12, No. 1.
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AU - Colombino, Maria

AU - Sini, MariaCristina

AU - Lissia, Amelia

AU - De Giorgi, Vincenzo

AU - Stanganelli, Ignazio

AU - Ayala, Fabrizio

AU - Massi, Daniela

AU - Rubino, Corrado

AU - Manca, Antonella

AU - Paliogiannis, Panagiotis

AU - Rossari, Susanna

AU - Magi, Serena

AU - Mazzoni, Laura

AU - Botti, Gerardo

AU - Capone, Mariaelena

AU - Palla, Marco

AU - Ascierto, Paolo A.

AU - Cossu, Antonio

AU - Palmieri, Giuseppe

AU - Caracò, C.

AU - Chiarion Sileni, V.

AU - Mozzillo, N.

AU - Queirolo, P.

AU - Rossi, C. R.

AU - Testori, A.

PY - 2014/5/8

Y1 - 2014/5/8

N2 - Background: Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).Methods: One hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N = 229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications. Results: BRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p <0.001) and CyclinD1 (p = 0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors.Conclusions: The low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.

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KW - Gene amplification

KW - Melanomagenesis

KW - Molecular classification

KW - Multiple melanoma

KW - Mutation analysis

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