57º Congresso Brasileiro de Genética
Resumos do 57º Congresso Brasileiro de Genética • 30 de agosto a 2 de setembro de 2011
Centro de Convenções do Hotel Monte Real Resort • Águas de Lindóia • SP • Brasil
www.sbg.org.br - ISBN 978-85-89109-06-2
307
TP53 PIN3 polymorphism analysis in cancer
patients who meet clinical criteria for LiFraumeni-Like Syndrome
Alemar, B1,3; Fitarelli-Kiehl, M1,3; Giacomazzi, J2,3; Cossio, SL3,5; Paskulin, DA1,3; Macedo, G1,3; Brunetto, A4; Selistre,
S4; Camey, SA6; Ashton-Prolla, P3.
1.PPG em Genética e Biologia Molecular - Universidade Federal do Rio Grande do Sul, 2.PPG em Medicina: Ciências
Médicas - Universidade Federal do Rio Grande do Sul, 3.Laboratório de Medicina Genômica, Centro de Pesquisa
Experimental – Hospital de Clínicas de Porto Alegre, 4.Serviço de Oncologia Pediátrica – Hospital de Clínicas de Porto
Alegre, 5.Pós Doutorado InaGemp, 6.Instituto de Matemática – Departamento de Estatística – Universidade Federal do
Rio Grande do Sul
Keywords: Li-Fraumeni Syndrome, TP53 germline mutations, PIN3 polymorphism
Li-Fraumeni Syndrome (LFS) and its variant Li-Fraumeni-like (LFL) are autosomal dominant cancer predisposition
syndromes associated to the occurrence of multiple tumors at young age and to germline TP53 mutations. In TP53
mutation-positive individuals with LFS/LFL, the presence of a 16 bp duplication in intron 3 (PIN3) of the gene is
associated with delayed diagnosis of cancer with a difference of up to 19 years compared to patients without the duplication. In this study, we evaluated the distribution of TP53 PIN3 in 25 patients with and without TP53 mutations,
affected by cancer and with the clinical diagnosis of LFL, recruited from the Pediatric Oncology ambulatory, located
in Hospital de Clínicas de Porto Alegre. Genomic DNA was extracted from peripheral blood. Analysis of intron 3
was performed by PCR followed by direct sequencing. Ten patients had germline TP53 mutations and 15 did not.
The frequencies of the PIN3 alleles N (not duplicated) and D (duplicated) were estimated at 0.95 and 0.05 in patients
with mutations, respectively, and 0.90 and 0.10 in patients without identified mutations in TP53. In the group with
mutations, the mean age at cancer diagnosis was 5.6 years for patients with genotype NN and 6 years for those with
an ND PIN3 genotype. In the group without identified mutations, the mean age at cancer diagnosis was 8.1 years
for NN and 12 years for ND and DD genotypes. The allele frequencies did not differ significantly (P=0.19) between
patients with and without TP53 mutations. Furthermore, the mean age at cancer diagnosis did not differ between
patients with different genotypes (P=0.19). However, there is an apparent trend of older age at cancer diagnosis in
patients with PIN3 genotypes DD or ND, regardless of the TP53 mutational status, which should be confirmed in a
larger series of cases.