The P48T germline mutation and polymorphism in the CDKN2A gene of patients with melanoma
Braz. j. med. biol. res
;
39(2): 237-241, Feb. 2006. ilus, tab
Artigo
em Inglês
| LILACS
| ID: lil-420275
RESUMO
CDKN2A has been implicated as a melanoma susceptibility gene in some kindreds with a family history of this disease. Mutations in CDKN2A may produce an imbalance between functional p16ink4a and cyclin D causing abnormal cell growth. We searched for germline mutations in this gene in 22 patients with clinical criteria of hereditary cancer (early onset, presence of multiple primary melanoma or 1 or more first- or second-degree relatives affected) by secondary structural content prediction, a mutation scanning method that relies on the propensity for single-strand DNA to take on a three-dimensional structure that is highly sequence dependent, and sequencing the samples with alterations in the electrophoretic mobility. The prevalence of CDKN2A mutation in our study was 4.5 percent (1/22) and there was a correlation between family history and probability of mutation detection. We found the P48T mutation in 1 patient with 2 melanoma-affected relatives. The patient descends from Italian families and this mutation has been reported previously only in Italian families in two independent studies. This leads us to suggest the presence of a mutational "hotspot" within this gene or a founder mutation. We also detected a high prevalence (59.1 percent) of polymorphisms, mainly alleles 500 C/G (7/31.8 percent) or 540 C/T (6/27.3 percent), in the 3' untranslated region of exon 3. This result reinforces the idea that these rare polymorphic alleles have been significantly associated with the risk of developing melanoma.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Polimorfismo Genético
/
Neoplasias Cutâneas
/
Mutação em Linhagem Germinativa
/
Melanoma
Tipo de estudo:
Estudo prognóstico
/
Fatores de risco
Limite:
Adolescente
/
Adulto
/
Idoso
/
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2006
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
Universidade de São Paulo/BR
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