http://www.cnr.it/ontology/cnr/individuo/prodotto/ID15086
BRAF gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup study (Articolo in rivista)
- Type
- Label
- BRAF gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup study (Articolo in rivista) (literal)
- Anno
- 2004-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1200/JCO.2004.07.112 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Casula M; Colombino M; Satta MP; Cossu A; Ascierto PA; Bianchi-Scarrà G; Castiglia D; Budroni M; Rozzo C; Manca A; Lissia A; Carboni A; Petretto E; Satriano SMR; Botti G; Mantelli M; Ghiorzo P; Stratton MR; Tanda F; Palmieri G. (literal)
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- ISI Web of Science (WOS) (literal)
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- C.N.R. Istituto di chimica biomolecolare, sede di Sassari
Università di Sassari, Istituto di Anatomia Patologica
Istituto Nazionale Tumori, Fondazione G Pascale, Napoli
Università di Genova, Dipartimento Oncologia Biologia & Genetica
IRCCS, Istituto Dermopatico dell'Immacolata, Roma
Centro Osservazione Epidemiologica Multizonale, Sassari (literal)
- Titolo
- BRAF gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup study (literal)
- Abstract
- Purpose Oncogenic activation of the BRAF gene has been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). In this study, we investigated the contribution of BRAF to melanoma susceptibility, also making a comparison with frequency of CDKN2A germline mutations in MM patients from different areas in Italy.
Patients and Methods Using a combination of denaturing high-performance liquid chromatography analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 MM patients (211 from northern Italy and 358 from southern Italy) were screened for BRAF mutations.
Results Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in four (0.7%) of 569 MM patients. The most common BRAF mutation, V599E, was detected in one germline DNA sample only; M116R and G608H were newly described mutations. A high frequency (59%) of BRAF mutations was instead observed in tumor Samples from patients also undergoing germline DNA analysis; at the somatic level, substitution of valine 599 was found to account for the majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively collected patient samples originating in southern Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected.
Conclusion Mutation analysis of either blood DNA from a large collection of MM patients or matched MM tissues from a subset of such patients revealed that BRAF is somatically mutated and does not play a major role in melanoma susceptibility. The present study further suggests that patient origin may account for different mutation rates in candidate genes. (literal)
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