Gianna Carvalheira | Universidade Federal de São Paulo (UNIFESP) (original) (raw)

Papers by Gianna Carvalheira

Genes & Diseases, 2024

Transcriptomic analysis reveals that NIBAN1 overexpression is associated with BRAF V600E mutation... more Transcriptomic analysis reveals that NIBAN1 overexpression is associated with BRAF V600E mutation and increases the aggressiveness of thyroid cancer NIBAN1 overexpression has been reported in a wide range of thyroid carcinoma subtypes, and in other cancers, while it is not expressed in thyroid benign lesions and normal thyroid. 1e3 However, the mechanism associated with its expression and prognostic value remains unclear. In this study, six independent cohorts were enrolled, in which NIBAN1 expression was evaluated. A total of 583 patients with thyroid tumors, 326 patients with skin cancers, 293 patients with colorectal carcinoma, and 189 patients with lung carcinoma were analyzed. Our study demonstrates, for the first time, that NIBAN1 expression varied according to thyroid tumor subtypes, presence of BRAF V600E mutation, worse clinical features, and aggressive phenotype. Remarkably, the data suggest that BRAF V600E mutation might influence NIBAN1 expression in an MYC-dependent manner during the thyroid carcinogenic process. Furthermore, NIBAN1 expression was predicted to be associated with stress-induced transcription/translation. In summary, our findings suggested that NIBAN1 expression could be used not only to help preoperative diagnosis of a thyroid nodule but also may have prognostic implications. NIBAN1 expression levels were assessed in three differentiated thyroid tumors cohorts: (i) 52 thyroid samples, analyzed by RT-qPCR (RT-qPCR_BR) from the Brazilian cohort; (ii) 27 thyroid samples, assessed by RNA-Seq (RNA-Seq_BR) from the Brazilian cohort; and (iii) 504 patients with PTC from TCGA cohort (TCGA-THCA). In the RT-qPCR_BR and RNA-Seq_BR cohorts, NIBAN1 expression was highest in classical PTC (CVPTC), followed by follicular carcinoma (FTC) and follicular subtype of PTC (FVPTC) (Fig. 1A, B). In the RNA-Seq_BR cohort, NIBAN1 expression differed between CVPTC and FVPTC (Fig. 1B). In the TCGA-Peer review under responsibility of Chongqing Medical University.

Acta Botanica Brasilica, Dec 1, 1991

Recebido em 12/09/91. Aceito em 30/01/92 RESUMO: Neste trabalho são apresentados os números cromo... more Recebido em 12/09/91. Aceito em 30/01/92 RESUMO: Neste trabalho são apresentados os números cromossômicos observados em 22 espécies pertencentes a 19 gêneros de angiospermas coletadas em Pernambuco. Os dados principais foram resumidos em uma tabela incluindo referências de herbário, locais de coleta, números diplóides e determinações cromossômicas prévias. Para oito espécies não encontramos nenhuma referência anterior na literatura específica. Por outro lado, alguns autores têm relatado números cromossômicos diferentes para uma mesma espécie. Nossas observações sugerem que essas discordâncias, em geral, podem ser atri buídas à ocorrência, nessas espécies, de cromossomos satelitadoscom constrições secundárias elásticas. Caracterírticas citogenéticas especiais, observadas em algumas espécies, são também apresentadas e discutidas. Palavras-chave: Números cromossômicos, Angiospermae. ABSTRACI': Chromosome numbers are reported for 22 species belonging to 19 genera of angiosperms collected in the State of Pernambuco. A table with the herbarium voucher, collectingsites, diploid numbers and previous chromosomes counts for ali the species is presented. Eight of the species have no previous counts. For some species, two or more different chromosome numbers have been presented in the li terature. Our data suggest that most of such disagreements might be due to thepresence of satellited chromosomes with elastic secondary cbnstriction. Furthermore, special cytogenetics features of every species are hereby presented and discussed.

Cytogenetic and Genome Research, 2016

Journal of Heredity, 1994

V&V Editora eBooks, Oct 1, 2022

A Fenilcetonúria é uma doença genética rara e hereditária. Sua prevalência global é de 1:10.000 n... more A Fenilcetonúria é uma doença genética rara e hereditária. Sua prevalência global é de 1:10.000 nascidos vivos e no Brasil a incidência varia de 1: 15.000 a 1: 25.000. Apesar do Brasil ser um país com alta prevalência da doença, 62% dos responsáveis por crianças com Fenilcetonúria afirmaram que o sistema de saúde não está preparado para lidar com a doença. Para tentar mitigar a falta de informação, foi elaborado um jogo, chamado Fenilcetofood, para participantes maiores de 10 anos, cujo objetivo é fornecer dados sobre este acometimento, de forma lúdica e dinâmica, democratizando o acesso e promovendo a inclusão.

Front Cell Dev Biol. , 2022

Cell survival must quickly activate specific mechanisms that enable to detect changes in the cell... more Cell survival must quickly activate specific mechanisms that enable to detect changes in the cellular microenvironment. The impact of these cell alteration has direct consequences on cellular homeostasis. Cellular stress, as well as its regulation and implication, has been studied in different pathologies. In this sense, the alteration in NIBAN1 expression seems to act in response to different cellular disturbances. Over the years, the knowledge of NIBAN1 functions has improved, demonstrating its important cell roles, favoring the cell survival under stress context. In response to the disturbances, NIBAN1 seems to be involved in the decision-making process between cell survival and death. The increase in NIBAN1 expression has been related to cellular mechanisms that seek to minimize the damage caused to cellular homeostasis. In this review, the main biological insights attributed to the NIBAN1 gene in different cellular contexts and its role as a mediator of cellular stress are discussed.

Pediatric Blood & Cancer, 2019

Background: The incidence of thyroid carcinoma has increased in most populations, including pedia... more Background: The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen-activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiationexposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. Procedure: In this study, we investigated the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK-BRAF fusion was investigated by RT-PCR and confirmed by FISH break-apart. The BRAF V600E mutation was screened using Sanger sequencing. Results: AGK-BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. Conclusion: Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.

Journal of the Endocrine Society, 2017

Thyrotoxic periodic paralysis (TPP) is a life-threatening neuromuscular complication of thyrotoxi... more Thyrotoxic periodic paralysis (TPP) is a life-threatening neuromuscular complication of thyrotoxicosis characterized by muscle weakness and hypokalemia and with an unclear etiopathogenesis. However, the 17q24.3 locus had been genetically linked to TPP, in which the genetic variant rs312691 (TC genotype) in long intergenic noncoding RNA (lincRNA) CTD-2378E21.1 is located downstream of inward-rectifier potassium (Kir) channel genes [KCNJ2 and its antisense KCNJ2 (AS-KCNJ2)]. A TPP patient with a suppressed thyroid-stimulating hormone level, a high free thyroxine level of (5.8 ng/dL), and low serum potassium level of (2 mEq/L) was evaluated for Kir channel expression during and after recovery from thyrotoxicosis. We observed that circulating lincRNA and Kir expression varied in accordance with thyroid status and TC genotype. To endorse this association of a lincRNA-rs312691 variant with a genetic risk of TPP, an additional series of 37 patients with TPP and 32 patients with thyrotoxic ...

Meta Gene, 2014

Rearrangements in chromosome 19 are rare. Among the 35 patients with partial 19q trisomy describe... more Rearrangements in chromosome 19 are rare. Among the 35 patients with partial 19q trisomy described, only six have a breakpoint defined by array. The 19q duplication results in a variable phenotype, including dysmorphisms, intellectual disability and seizure. In a female patient, although G-banding at 550 band-resolution was normal, multiplex ligation-dependent probe amplification (MLPA) technique and genomic array showed a 10.6 Mb terminal duplication of chromosome 19q13. Fluorescent in situ hybridization (FISH) revealed that the duplicated region was attached to the short arm of chromosome 21 and silver staining showed four small acrocentrics with nucleolar organization region (NOR) activity, suggesting that the breakpoint in chromosome 21 was at p13. This is the first de novo translocation between 19q13.33 and 21p13 described in liveborn. The chromosome 19 is known to be rich in coding and non-coding regions, and chromosomal rearrangements involving this chromosome are very harmful. Furthermore, the 19q13.33→qter region is dense in pseudogenes and microRNAs, which are potent regulators of gene expression. The trisomic level of this region may contribute to deregulation of global gene expression, and consequently, may lead to abnormal development on the carriers of these rearrangements.

Journal of Oral Science, 2004

Frontiers in Cell and Developmental Biology

Frontiers in Genetics

Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsycholog... more Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsychological clinical spectrum. We hypothesized that the neurocognitive dysfunction present in KS relies on an imbalance in X-chromosome gene expression. Thus, the X-chromosome inactivation (XCI) pattern and neurocognitive X-linked gene expression were tested and correlated with intelligence quotient (IQ) scores. We evaluated 11 KS patients by (a) IQ assessment, (b) analyzing the XCI patterns using both HUMARA and ZDHHC15 gene assays, and (c) blood RT-qPCR to investigate seven X-linked genes related to neurocognitive development (GTPBP6, EIF2S3, ITM2A, HUWE1, KDM5C, GDI1, and VAMP7) and XIST in comparison with 14 (male and female) controls. Considering IQ 80 as the standard minimum reference, we verified that the variability in IQ scores in KS patients seemed to be associated with the XCI pattern. Seven individuals in the KS group presented a random X-inactivation (RXI) and lower average IQ than...

Journal of the Endocrine Society

Gonadal sex determination is a complex genetic process by which an embryonic primordium is driven... more Gonadal sex determination is a complex genetic process by which an embryonic primordium is driven to form an ovary or a testis, which requires a delicate dosage balance involving many genes. Disruption in this molecular pathway can lead to differences of sex development (DSD). Although some genetic mechanisms leading to 46,XY DSD have been elucidated, little is known about copy-number variation (CNV) causing testicular or ovotesticular 46,XX DSD. We describe a 20-year natural history of a man with SRY-negative 46,XX, who was born with atypical male external genitalia, aortic coarctation, and bilateral blepharophimosis-ptosis. The molecular study identified a de novo heterozygous 3-Mb 15q26.2 deletion, a gene-poor locus containing NR2F2, which encodes the nuclear receptor COUP-TFII that is highly expressed in ovary and cardiac arteries. Immunohistochemistry confirmed the low COUP-TFII expression on his ovotestis tissue. Monosomy of 15q26.2, encompassing the NR2F2 gene, may act as a Z...

Human Genetics

The 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent hemizygous deletions of chromoso... more The 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent hemizygous deletions of chromosome 22q11.2. The phenotype of the syndrome is complex and varies widely among individuals. Little is known about the role of the different genes located in 22q11.2, and we hypothesized that genetic risk factors lying elsewhere in the genome might contribute to the phenotype. Here, we present the whole-genome gene expression data of 11 patients with approximately 3 Mb deletions. Apart from the hemizygous genes mapped to the 22q11.2 region, the TUBA8 and GNAZ genes, neighboring the deleted interval but in normal copy number, showed altered expression. When genes mapped to other chromosomes were considered in the gene expression analysis, a genome-wide dysregulation was observed, with increased or decreased expression levels. The enriched pathways of these genes were related to immune response, a deficiency that is frequently observed in 22q11.2DS patients. We also used the hypothesis-free weighted gene co-expression network analysis (WGCNA), which revealed the co-expression gene network modules with clear connection to mechanisms associated with 22q11.2DS such as immune response and schizophrenia. These findings, combined with the traditional gene expression profile, can be used for the identification of potential pathways and genes not previously considered to be related to the 22q11.2 deletion syndrome.

Endocrine-Related Cancer

We previously proposed that high expression of FAM129A can be used as a thyroid carcinoma biomark... more We previously proposed that high expression of FAM129A can be used as a thyroid carcinoma biomarker in preoperative diagnostic exams of thyroid nodules. Here, we identify that FAM129A expression is increased under nutrient and growth factor depletion in a normal thyroid cell line (PCCL3), overlapping with increased expression of autophagy-related protein and inhibition of AKT/mTOR/p70S6K. Supplementation of insulin, TSH and serum to the medium was able to reduce the expression of both FAM129A and autophagy-related protein and reestablish the AKT/mTOR/p70S6K axis. To determine the direct role of FAM129A on autophagy, FAM129A was transfected into PCCL3 cells. Its overexpression induced autophagic vesicles formation, evidenced by transmission electron microscopy. Co-expression of FAM129A and mCherry-EGFP-LC3B in PCCL3 showed an increased yellow puncta formation, suggesting that FAM129Ainduces autophagy. To further confirm its role on autophagy, we knockdown FAM129A in two thyroid carci...

Human mutation, Feb 28, 2017

We report five individuals with loss-of-function of the X-linked AMMECR1: a girl with a balanced ... more We report five individuals with loss-of-function of the X-linked AMMECR1: a girl with a balanced X-autosome translocation and inactivation of the normal X-chromosome; two boys with maternally inherited and de novo nonsense variants; and two half-brothers with maternally inherited microdeletion variants. They present with short stature, cardiac and skeletal abnormalities, and hearing loss. Variants of unknown significance in AMMECR1 in four male patients from two families with partially overlapping phenotypes were previously reported. AMMECR1 is coexpressed with genes implicated in cell cycle regulation, five of which were previously associated with growth and bone alterations. Our knockdown of the zebrafish orthologous gene resulted in phenotypes reminiscent of patients' features. The increased transcript and encoded protein levels of AMMECR1L, an AMMECR1 paralog, in the t(X;9) patient's cells indicate a possible partial compensatory mechanism. AMMECR1 and AMMECR1L proteins ...