Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith-Magenis syndrome

Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene. Here we have evaluated 30 patients with suspected SMS and identified SMS-associated classical 17p11.2 deletions in six patients, an atypical deletion of ∼139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene nonsynonymous alterations of unknown significance in two unrelated patients. The RAI1 mutant proteins showed no significant alterations in molecular weight, subcellular localization and transcriptional activity. Clinical features of patients with or without 17p11.2 deletions and mutations involving the RAI1 gene were compared to identify phenotypes that may be useful in diagnosing patients with SMS. © 2012 Macmillan Publishers Limited All rights reserved.

Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

Objective: To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients. Methods: Tumors and their respective recurrences, six low-grade and five high-grade cases, provided 19 samples that were submitted to laser microdissection capture followed by high resolution comparative genomic hybridization (HR-CGH). HR-CGH profiles went through two different analyses-all tumors combined or classified according to their respective histologic grades. In a supplementary analysis, 124 primary urothelial tumors, their recurrences, and normal urothelium biopsied during the period between tumor surgical resection and recurrence, were submitted to immunohistochemical analyses of the p53 protein. During the follow-up of at least 21 patients, urinary bladder washes citologically negative for neoplastic cells were submitted to fluorescence in situ hybridization (FISH) to detect copy number alterations in centromeres 7, 17, and 9p21 region. Results and Conclusions: HR-CGH indicated high frequencies (80%) of gains in 11p12 and losses in 16p12, in line with suggestions that these chromosome regions contain genes critical for urinary bladder carcinogenesis. Within a same patient, tumors and their respective recurrences showed common genomic losses and gains, which implies that the genomic profile acquired by primary tumors was relatively stable. There were exclusive genomic alterations in low and in high grade tumors. Genes mapped in these regions should be investigated on their involvement in the urinary bladder carcinogenesis. Successive tumors from same patient did not present similar levels of protein p53 expression; however, when cases were grouped according to tumor histologic grades, p53 expression was directly proportional to tumor grades. Biopsies taken during the follow-up of patients with history of previously resected UBC revealed that 5/15 patients with no histologic alterations had more than 25% of urothelial cells expressing the p53 protein, suggesting that the apparently normal urothelium was genomically unstable. No numerical alterations of the chromosomes 7, 17, and 9p21 region were found by FISH during the periods free-of-neoplasia. Our data are informative for further studies to better understand urinary bladder urothelial carcinogenesis. © 2013 Elsevier Inc.

Alterações no número de cópias genômicas em mastocitomas cutâneos caninos

Pós-graduação em Medicina Veterinária - FCAV

Contribuições ao conhecimento de cromossomos supernuméricos em peixes, utilizando como modelo Haplochromis obliquidens (Perciformes, Cichlidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Perfil de alterações genômicas em angiofibromas nasofaringeos juvenis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise da expressão dos genes STEAP1 e STEAP2 em adenocarcinomas de próstata por RT-PCR quantitativa em tempo real

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Perfil genômico do carcinoma de células escamosas de laringe e seu fronte de invasão

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterações genômicas na endometriose

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ganhos e perdas genômicas em momentos sucessivos do carcinoma urotelial de bexiga humana

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Alterações no número de cópias genômicas em carcinomas de mama

Pós-graduação em Ciências Biológicas (Genética) - IBB

ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

ROCK1 as a novel prognostic marker in vulvar cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Down-regulation of SLC8A1 as a putative apoptosis evasion mechanism by modulation of calcium levels in penile carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica

Pós-graduação em Patologia - FMB