Microallelotyping defines novel regions of loss of heterozygosity in uterine leiomyomas

Uterine leiomyomas are extremely common, benign, smooth muscle tumors that represent a significant public health problem. Although there have been few molecular studies of uterine leiomyomas, most of them have reported a very low frequency of loss of heterozygosity (LOH) in different regions of the genome. The detection of LOH has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types. We have used a set of 15 microsatellite polymorphism markers to examine the frequency of allele loss in a panel of 64 human uterine leiomyomas matched to normal DNAs. The markers were chosen from regions involved in losses identified by comparative genomic hybridization in a subset of uterine leiomyomas described in a previous report. DNA from tumors and normal tissue was amplified by the polymerase chain reaction and subsequently analyzed using an ABI Prism 377 DNA automated sequencer. The frequency of LOH observed was low, except for the markers D15S87 (15q26.3), D7S493 (7p15.3), and D7S517 (7p22.2). No changes in microsatellite size were detected in our samples. These results provide useful clues for identifying putative tumor suppressor genes associated with a subset of uterine leiomyomas. (C) 2004 Wiley-Liss, Inc.

Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites: the potential role of stem cells

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

Copy number variation of individual cattle genomes using next-generation sequencing

Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one Holstein, and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1265 CNV regions comprising similar to 55.6-Mbp sequence-476 of which (similar to 38%) have not previously been reported. We validated this sequence-based CNV call set with array comparative genomic hybridization (aCGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH), achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (similar to 52%, chi(2) test; P-value <0.05). In contrast, genes related to pathogen- and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and WC1, suggesting that some CNVs may be associated with breed-specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome-wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome.

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)