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 language | English |
|---|---|
| Article number | 202 |
| Journal | Journal of Translational Medicine |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Aug 29 2013 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84883104349&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883104349&partnerID=8YFLogxK
U2 - 10.1186/1479-5876-11-202
DO - 10.1186/1479-5876-11-202
M3 - Article
VL - 11
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
IS - 1
M1 - 202
ER -