Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma

Maria Colombino, Amelia Lissia, Mariaelena Capone, Vincenzo De Giorgi, Daniela Massi, Ignazio Stanganelli, Ester Fonsatti, Michele Maio, Gerardo Botti, Corrado Caracò, Nicola Mozzillo, Paolo A. Ascierto, Antonio Cossu, Giuseppe Palmieri

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Prevalence and distribution of pathogenetic mutations in BRAF and NRAS genes were evaluated in multiple melanoma lesions from patients with different geographical origin within the same Italian population.Methods: Genomic DNA from a total of 749 tumor samples (451 primary tumors and 298 metastases) in 513 consecutively-collected patients with advanced melanoma (AJCC stages III and IV) was screened for mutations in exon 15 of BRAF gene and, at lower extension (354/513; 69%), in the entire coding DNA of NRAS gene by automated direct sequencing. Among tissues, 236 paired samples of primary melanomas and synchronous or asynchronous metastases were included into the screening.Results: Overall, mutations were detected in 49% primary melanomas and 51% metastases, for BRAF gene, and 15% primary tumors and 16% secondaries, for NRAS gene. A heterogeneous distribution of mutations in both genes was observed among the 451 primary melanomas according to patients' geographical origin: 61% vs. 42% (p = 0.0372) BRAF-mutated patients and 2% vs. 21% (p <0.0001) NRAS-mutated cases were observed in Sardinian and non-Sardinian populations, respectively. Consistency in BRAF/NRAS mutations among paired samples was high for lymph node (91%) and visceral metastases (92.5%), but significantly lower for brain (79%; p = 0.0227) and skin (71%; p = 0.0009) metastases.Conclusions: Our findings about the two main alterations occurring in the different tumor tissues from patients with advanced melanoma may be helpful in improving the management of such a disease.

Original languageEnglish
Article number202
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - Aug 29 2013

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Melanoma
Genes
Mutation
Tumors
Neoplasm Metastasis
Neoplasms
Tissue
DNA
Population
Exons
Brain
Skin
Screening
Lymph Nodes

Keywords

  • BRAF gene
  • Cancer genetic heterogeneity
  • Malignant melanoma
  • Mutation analysis
  • NRAS gene

ASJC Scopus subject areas

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

Cite this

Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma. / Colombino, Maria; Lissia, Amelia; Capone, Mariaelena; De Giorgi, Vincenzo; Massi, Daniela; Stanganelli, Ignazio; Fonsatti, Ester; Maio, Michele; Botti, Gerardo; Caracò, Corrado; Mozzillo, Nicola; Ascierto, Paolo A.; Cossu, Antonio; Palmieri, Giuseppe.

In: Journal of Translational Medicine, Vol. 11, No. 1, 202, 29.08.2013.

Research output: Contribution to journalArticle

Colombino, M, Lissia, A, Capone, M, De Giorgi, V, Massi, D, Stanganelli, I, Fonsatti, E, Maio, M, Botti, G, Caracò, C, Mozzillo, N, Ascierto, PA, Cossu, A & Palmieri, G 2013, 'Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma', Journal of Translational Medicine, vol. 11, no. 1, 202. https://doi.org/10.1186/1479-5876-11-202
Colombino, Maria ; Lissia, Amelia ; Capone, Mariaelena ; De Giorgi, Vincenzo ; Massi, Daniela ; Stanganelli, Ignazio ; Fonsatti, Ester ; Maio, Michele ; Botti, Gerardo ; Caracò, Corrado ; Mozzillo, Nicola ; Ascierto, Paolo A. ; Cossu, Antonio ; Palmieri, Giuseppe. / Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma. In: Journal of Translational Medicine. 2013 ; Vol. 11, No. 1.
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abstract = "Background: Prevalence and distribution of pathogenetic mutations in BRAF and NRAS genes were evaluated in multiple melanoma lesions from patients with different geographical origin within the same Italian population.Methods: Genomic DNA from a total of 749 tumor samples (451 primary tumors and 298 metastases) in 513 consecutively-collected patients with advanced melanoma (AJCC stages III and IV) was screened for mutations in exon 15 of BRAF gene and, at lower extension (354/513; 69{\%}), in the entire coding DNA of NRAS gene by automated direct sequencing. Among tissues, 236 paired samples of primary melanomas and synchronous or asynchronous metastases were included into the screening.Results: Overall, mutations were detected in 49{\%} primary melanomas and 51{\%} metastases, for BRAF gene, and 15{\%} primary tumors and 16{\%} secondaries, for NRAS gene. A heterogeneous distribution of mutations in both genes was observed among the 451 primary melanomas according to patients' geographical origin: 61{\%} vs. 42{\%} (p = 0.0372) BRAF-mutated patients and 2{\%} vs. 21{\%} (p <0.0001) NRAS-mutated cases were observed in Sardinian and non-Sardinian populations, respectively. Consistency in BRAF/NRAS mutations among paired samples was high for lymph node (91{\%}) and visceral metastases (92.5{\%}), but significantly lower for brain (79{\%}; p = 0.0227) and skin (71{\%}; p = 0.0009) metastases.Conclusions: Our findings about the two main alterations occurring in the different tumor tissues from patients with advanced melanoma may be helpful in improving the management of such a disease.",
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T1 - Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma

AU - Colombino, Maria

AU - Lissia, Amelia

AU - Capone, Mariaelena

AU - De Giorgi, Vincenzo

AU - Massi, Daniela

AU - Stanganelli, Ignazio

AU - Fonsatti, Ester

AU - Maio, Michele

AU - Botti, Gerardo

AU - Caracò, Corrado

AU - Mozzillo, Nicola

AU - Ascierto, Paolo A.

AU - Cossu, Antonio

AU - Palmieri, Giuseppe

PY - 2013/8/29

Y1 - 2013/8/29

N2 - Background: Prevalence and distribution of pathogenetic mutations in BRAF and NRAS genes were evaluated in multiple melanoma lesions from patients with different geographical origin within the same Italian population.Methods: Genomic DNA from a total of 749 tumor samples (451 primary tumors and 298 metastases) in 513 consecutively-collected patients with advanced melanoma (AJCC stages III and IV) was screened for mutations in exon 15 of BRAF gene and, at lower extension (354/513; 69%), in the entire coding DNA of NRAS gene by automated direct sequencing. Among tissues, 236 paired samples of primary melanomas and synchronous or asynchronous metastases were included into the screening.Results: Overall, mutations were detected in 49% primary melanomas and 51% metastases, for BRAF gene, and 15% primary tumors and 16% secondaries, for NRAS gene. A heterogeneous distribution of mutations in both genes was observed among the 451 primary melanomas according to patients' geographical origin: 61% vs. 42% (p = 0.0372) BRAF-mutated patients and 2% vs. 21% (p <0.0001) NRAS-mutated cases were observed in Sardinian and non-Sardinian populations, respectively. Consistency in BRAF/NRAS mutations among paired samples was high for lymph node (91%) and visceral metastases (92.5%), but significantly lower for brain (79%; p = 0.0227) and skin (71%; p = 0.0009) metastases.Conclusions: Our findings about the two main alterations occurring in the different tumor tissues from patients with advanced melanoma may be helpful in improving the management of such a disease.

AB - Background: Prevalence and distribution of pathogenetic mutations in BRAF and NRAS genes were evaluated in multiple melanoma lesions from patients with different geographical origin within the same Italian population.Methods: Genomic DNA from a total of 749 tumor samples (451 primary tumors and 298 metastases) in 513 consecutively-collected patients with advanced melanoma (AJCC stages III and IV) was screened for mutations in exon 15 of BRAF gene and, at lower extension (354/513; 69%), in the entire coding DNA of NRAS gene by automated direct sequencing. Among tissues, 236 paired samples of primary melanomas and synchronous or asynchronous metastases were included into the screening.Results: Overall, mutations were detected in 49% primary melanomas and 51% metastases, for BRAF gene, and 15% primary tumors and 16% secondaries, for NRAS gene. A heterogeneous distribution of mutations in both genes was observed among the 451 primary melanomas according to patients' geographical origin: 61% vs. 42% (p = 0.0372) BRAF-mutated patients and 2% vs. 21% (p <0.0001) NRAS-mutated cases were observed in Sardinian and non-Sardinian populations, respectively. Consistency in BRAF/NRAS mutations among paired samples was high for lymph node (91%) and visceral metastases (92.5%), but significantly lower for brain (79%; p = 0.0227) and skin (71%; p = 0.0009) metastases.Conclusions: Our findings about the two main alterations occurring in the different tumor tissues from patients with advanced melanoma may be helpful in improving the management of such a disease.

KW - BRAF gene

KW - Cancer genetic heterogeneity

KW - Malignant melanoma

KW - Mutation analysis

KW - NRAS gene

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