ERICKA BARBOSA TRARBACH
Projetos de Pesquisa
Unidades Organizacionais
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
bookPart Biologia molecular dos tumores endócrinos(2013) LERARIO, Antonio Marcondes; FRAGOSO, Maria Candida Barisson; BRITO, Luciana Pinto; MARTIN, Regina Matsunaga; TRARBACH, Erika Barbosa; MARUI, Suemi; TOLEDO, Rodrigo de Almeida; DOMENICE, Sorahia; MENDONçA, Berenice Bilharinho deconferenceObject Molecular Investigation of PTEN and DREAM Genes in Patients with Multinodular Goiter(2014) SHINZATO, Amanda; LERARIO, Antonio M.; DANILOVIC, Debora Lucia Seguro; LIN, Chin Jia; MARUI, Suemi; TRARBACH, Ericka Barbosa- Transcriptome analysis showed a Differential signature between invasive and non-invasive corticotrophinomas(2017) ARAUJO, Leonardo Jose Tadeu de; LERARIO, Antonio Marcondes; CASTRO, Margaret de; MARTINS, Clarissa Silva; BRONSTEIN, Marcello Delano; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; FRAGOSO, Maria Candida Barisson VillaresACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushing's disease (CD)] is the most common cause of endogenous Cushing's syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (approximate to 80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, >= 10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also identified potential biological pathways associated with growth and invasiveness, TGF-beta and G protein signaling pathways, DNA damage response pathway, and pathways associated with focal adhesion. Our study revealed a differential pattern of genetic signature in a subgroup of MAC, supporting a genetic influence on corticotrophinomas in patients with CD.
conferenceObject Targeted High-Throughput Sequencing of RAS/MAPK Pathway Genes for Diagnosis of Noonan Syndrome (NS) and Noonan-Related Disorders (NRD)(2014) MALAQUIAS, Alexsandra C.; MORAES, Michelle B.; LERARIO, Antonio M.; TRARBACH, Ericka Barbosa; MITNE-NETO, Miguel; PEREIRA, Alexandre; BERTOLA, Debora R.; TELES, Milena Gurgel; JORGE, Alexander Augusto Lima- New genetic findings in a large cohort of congenital hypogonadotropic hypogonadism(2019) AMATO, Lorena Guimaraes Lima; MONTENEGRO, Luciana Ribeiro; LERARIO, Antonio Marcondes; JORGE, Alexander Augusto Lima; GUERRA JUNIOR, Gil; SCHNOLL, Caroline; RENCK, Alessandra Covallero; TRARBACH, Ericka Barbosa; COSTA, Elaine Maria Frade; MENDONCA, Berenice Bilharinho; LATRONICO, Ana Claudia; SILVEIRA, Leticia Ferreira GontijoContext: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. Several genes have been associated with the pathogenesis of CHH, but most cases still remain without a molecular diagnosis. The advent of next-generation sequencing (NGS) has allowed the simultaneous genotyping of several regions, faster, making possible the extension of the genetic knowledge of CHH. Objective: Genetic characterization of a large cohort of Brazilian CHH patients. Design and patients: A cohort of 130 unrelated patients (91 males, 39 females) with CHH (75 normosmic CHH, 55 Kallmann syndrome) was studied using a panel containing 36 CHH-associated genes. Results: Potential pathogenic or probably pathogenic variants were identified in 43 (33%) CHH patients. The genes ANOS1, FGFR1 and GNRHR were the most frequently affected. A novel homozygous splice site mutation was identified in the GNRH1 gene and a deletion of the entire coding sequence was identified in SOX10. Deleterious variants in the IGSF10 gene were identified in two patients with reversible normosmic CHH. Notably, 6.9% of the patients had rare variants in more than one gene. Rare variants were also identified in SPRY4, IL17RD, FGF17, IGSF1 and FLRT3 genes. Conclusions: This is a large study of the molecular genetics of CHH providing new genetic findings for this complex and heterogeneous genetic condition. NGS has been shown to be a fast, reliable and effective tool in the molecular diagnosis of congenital CHH and being able to targeting clinical genetic testing in the future.
conferenceObject Molecular Investigation of PTEN and DREAM Genes in Patients with Multinodular Goiter(2014) SHINZATO, Amanda; LERARIO, Antonio M.; DANILOVIC, Debora Lucia Seguro; LIN, Chin Jia; MARUI, Suemi; TRARBACH, Ericka Barbosa- New Insights Into Pheochromocytoma Surveillance of Young Patients With VHL Missense Mutations(2019) FAGUNDES, Gustavo F. C.; PETENUCI, Janaina; JR, Delmar M. Lourenco; TRARBACH, Ericka B.; PEREIRA, Maria Adelaide A.; D'EUR, Joya Emilie Correa; HOFF, Ana O.; LERARIO, Antonio M.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose Luis; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.Context: Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. Objective: Genotype-phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. Design: We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. Results: PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-yearold boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. Conclusion: VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.
- Evaluation of Downstream Regulatory Element Antagonistic Modulator Gene in Human Multinodular Goiter(2015) SHINZATO, Amanda; LERARIO, Antonio M.; LIN, Chin J.; DANILOVIC, Debora S.; MARUI, Suemi; TRARBACH, Ericka B.Background: DREAM (Downstream Regulatory Element Antagonistic Modulator) is a neuronal calcium sensor that was suggested to modulate TSH receptor activity and whose overexpression provokes an enlargement of the thyroid gland in transgenic mice. The aim of this study was to investigate somatic mutations and DREAM gene expression in human multinodular goiter (MNG). Material/Methods: DNA and RNA samples were obtained from hyperplastic thyroid glands of 60 patients (54 females) with benign MNG. DREAM mutations were evaluated by PCR and direct automatic sequencing, whereas relative quantification of mRNA was performed by real-time PCR. Over-and under-expression were defined as a 2-fold increase and decrease in comparison to normal thyroid tissue, respectively. RQ M (relative quantification mean); SD (standard deviation). Results: DREAM expression was detected in all nodules evaluated. DREAM mRNA was overexpressed in 31.7% of MNG (RQ M=6.26; SD=5.08), whereas 53.3% and 15% had either normal (RQ M=1.16; SD=0.46) or underexpression (RQ M=0.30; SD=0.10), respectively. Regarding DREAM mutations analysis, only previously described intronic polymorphisms were observed. Conclusions: We report DREAM gene expression in the hyperplastic thyroid gland of MNG patients. However, DREAM expression did not vary significantly, and was somewhat underexpressed in most patients, suggesting that DREAM upregulation does not significantly affect nodular development in human goiter.
- Transcriptome Analysis Showed a Differential Signature Between Invasive and Non-invasive Corticotrophinomas (vol 8, 55, 2017)(2019) ARAUJO, Leonardo Jose Tadeu de; LERARIO, Antonio Marcondes; CASTRO, Margaret de; MARTINS, Clarissa Silva; BRONSTEIN, Marcello Delano; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; FRAGOSO, Maria Candida Barisson Villares