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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

AUTHORS

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

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. More... »

PAGES

202

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1479-5876-11-202

DOI

http://dx.doi.org/10.1186/1479-5876-11-202

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023601025

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23987572


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