Association of TP53 polymorphisms on the risk of Wilms tumor.

BACKGROUND: Molecular factors influencing Wilms tumor (WT) development remain largely unknown. TP53 mutations seem to be restricted to the anaplastic WT subtype. However, TP53 polymorphisms do not have a defined role in the disease. PROCEDURE: To assess the impact of TP53 mutations and polymorphisms (PIN2, PIN3, and PEX4) on risk of development, age at diagnosis, and survival in WT, we analyzed 46 blood DNA samples and 31 fresh tumor DNA samples from 52 patients with WT. Sequencing of TP53 exons 2-11 was performed. RESULTS: Tumor DNA analysis revealed TP53 pathogenic missense mutations (p.V197M, p.R213Q, p.R248W, and p.R337C) in four samples (12.9%). Blood DNA samples revealed a novel intronic mutation, IVS2 + 37C > T, in one patient (2.2%). Bilaterality was associated with a twofold decrease in survival (P = 0.00037). Diffuse anaplasia also presented a lower survival probability compared to patients with non-anaplastic tumors, or with focal anaplasia (P = 0.045). Patients with a TP53 somatic mutation showed survival probability of 37.5% versus 85.0% for patients with no somatic mutations, although the difference was not statistically significant (P = 0.0706). PIN3 duplicated allele was associated with a 20-month later mean age at diagnosis (P = 0.0084). TP53 PEX4 C allele showed an increased risk for WT development (P = 0.0379). No relationship was found between survival and gender, age at diagnosis, or the less frequent alleles of PIN2, PIN3, and PEX4. CONCLUSIONS: Our results demonstrate an association between PIN3 and age at diagnosis, as well as an association of PEX4 and risk of development of WT.

Report of the second international symposium on molecular epidemiology in childhood leukaemia and embryonal tumours, Rio de Janeiro, Brazil.

The recent International Symposium on Molecular epidemiology in Embryonal Tumours and Paediatric Leukaemia was held on 4-6 March 2008 in Rio de Janeiro, Brazil. It proved a very productive meeting in which studies relating to genetics, therapeutical trials, identification of risk factors in acute leukaemia neuroblastoma and Wilms' tumours were presented. Over 120 participants gathered for three days of fruitful discussions, including representatives of paediatrics, haematology, laboratory, epidemiology and pathology. Debates were held about strategies of applications of important biomarkers for clinical trials. Highlights of each of the scientific presentations are summarized below.

Report of the second International Symposium on molecular epidemiology in childhood leukaemia and embryonal tumorus rio de janeiro Brazil

The recent International Symposium on Molecular epidemiology in Embryonal Tumours and Paediatric Leukaemia was held on 4–6 March 2008 in Rio de Janeiro, Brazil. It proved a very productive meeting in which studies relating to genetics, therapeutical trials, identification of risk factors in acute leukaemia neuroblastoma and Wilms’ tumours were presented. Over 120 participants gathered for three days of fruitful discussions, including representatives of paediatrics, haematology, laboratory, epidemiology and pathology. Debates were held about strategies of applications of important biomarkers for clinical trials. Highlights of each of the scientific presentations are summarized below.

Identification of three novel RB1 mutations in Brazilian patients with retinoblastoma by "exon by exon" PCR mediated SSCP analysis.

AIMS: To carry out a retrospective study, screening for mutations of the entire coding region of RB1 and adjacent intronic regions in patients with retinoblastoma. METHODS: Mutation screening in DNA extracts of formalin fixed, paraffin wax embedded tissues of 28 patients using combined "exon by exon" polymerase chain reaction mediated single strand conformational polymorphism analysis, followed by DNA sequencing. RESULTS: Eleven mutations were found in 10 patients. Ten mutations consisted of single base substitutions; 10 were localised in exonic regions (eight nonsense, one missense, and one frameshift) and another one in the intron-exon splicing region. Three novel mutations were identified: a 2 bp insertion in exon 2 (g.5506-5507insAG, R73fsX77), a G to A transition affecting the last invariant nucleotide of intron 13 (g.76429G>A), and a T to C transition in exon 20 (g.156795T>C, L688P). In addition, eight C to T transitions, resulting in stop codons, were found in five different CGA codons (g.64348C>T, g.76430C>T, g.78238C>T, g.78250C>T, and g.150037C>T). Although specific mutation hotspots have not been identified in the literature, eight of the 11 mutations occurred in CGA codons and seven fell within the E1A binding domains (codons 393-572 and 646-772), whereas five were of both types-in CGA codons within E1A binding domains. CONCLUSIONS: CGA codons and E1A binding domains are apparently more frequent mutational targets and should be initially screened in patients with retinoblastoma. Paraffin wax embedded samples proved to be valuable sources of DNA for retrospective studies, providing useful information for genetic counselling.

Acidente vascular cerebral em doenca falciforme. / Cerebrovascular accidents in sickle cell disease

Em revisao de 73 casos de doenca falciforme, acompanhados pelo Setor de Hematologia Infantil do Servico de Pediatria do Hospital dos Servidores do Estado (INAMPS), foram observados seis casos de AVC, significando um percentual de 8,2%.A idade em que ocorreu a complicacao neurologica variou de 10 meses a 13 anos. Quatro dos seis casos foram submetidos a tomografia computadorizada do cranio na epoca do AVC. Dos seis, tres tiveram recorrencia neurologica O tempo decorrido entre o primeiro AVC e a recidiva foi de seis meses em dois casos e 11 anos em outro. Quatro pacientes apresentaram sequelas neurologicas significativas. E discutida a indicacao de terapeutica com transfusoes de sangue periodicas e por longo prazo, com a finalidade de evitar a recidiva