Abstract The LEF1/TCF transcription factor family is related to the development of diverse tissue types, including the mammary tissue, and dysregulation of its expression and function has been described to favor breast tumorigenesis. However, the clinical and biological relevance of this gene family in breast cancer is still poorly understood. Here, we used bioinformatics approaches aiming to reduce this gap. We investigated its expression patterns in molecular and immune breast cancer subtypes; its correlation with immune cell infiltration, and its prognostic values in predicting outcomes. Also, through regulons construction, we determined the genes whose expression is influenced by these transcription factors, and the pathways in which they are involved. We found that LEF1 and TCF3 are over-expressed in breast tumors regarding non-tumor samples, while TCF4 and TCF7 are down-expressed, with the gene’s methylation status being associated with its expression dysregulation. All four transcription factors presented significance at the diagnostic and prognostic levels. LEF1, TCF4, and TCF7 presented a significant correlation with immune cell infiltration, being associated with the immune subtypes of less favorable outcomes. Altogether, this research contributes to a more accurate understanding of the expression and clinical and biomarker significance of the LEF1/TCF transcription factors in breast cancer. LEF1TCF LEFTCF TCF LEF types tumorigenesis However understood Here gap infiltration outcomes Also construction involved overexpressed over expressed nontumor non tumor samples downexpressed, downexpressed down expressed, down-expressed s levels Altogether

Abstract Male breast cancer (MBC) is a rare malignancy that accounts for about 1.8% of all breast cancer cases. In contrast to the high number of the “omics” studies in breast cancer in women, only recently molecular approaches have been performed in MBC research. High-throughput proteomics based methodologies are promisor strategies to characterize the MBC proteomic signatures and their association with clinico-pathological parameters. In this study, the label-free quantification-mass spectrometry and bioinformatics approaches were applied to analyze the proteomic profiling of a MBC case using the primary breast tumor and the corresponding axillary metastatic lymph nodes and adjacent non-tumor breast tissues. The differentially expressed proteins were identified in the signaling pathways of granzyme B, sirtuins, eIF2, actin cytoskeleton, eNOS, acute phase response and calcium and were connected to the upstream regulators MYC, PI3K SMARCA4 and cancer-related chemical drugs. An additional proteomic comparative analysis was performed with a primary breast tumor of a female patient and revealed an interesting set of proteins, which were mainly involved in cancer biology. Together, our data provide a relevant data source for the MBC research that can help the therapeutic strategies for its management.

Abstract Breast cancer (BC) is a heterogeneous disease, and it is the leading cause of death among women. NORAD and HCG11 are highly similar lncRNAs that present binding sites for PUMILIO proteins. PUMILIO acts on hundreds of mRNA targets, contributing to the modulation of gene expression. We analyzed the expression levels of NORAD and HCG11 in the BC subtypes luminal A (LA) and basal-like (BL), and the regulatory networks associated with these lncRNAs. In the analysis of TCGA cohort (n=329) and Brazilian BC samples (n=44), NORAD was up-regulated in LA while HCG11 was up-regulated in BL subtype. An increased expression of NORAD is associated with reduced disease-free survival in basal-like patients (p = 0.002), which suggests that its prognostic value could be different in specific subtypes. The biological pathways observed for the HCG11 network are linked to the epithelial-to-mesenchymal transition; while NORAD associated pathways appear to be related to luminal epithelial cell transformation. NORAD and HCG11 regulons respectively present 36% and 21.5% of PUMILIO targets, which suggests that these lncRNAs act as a decoy for PUMILIO. These lncRNAs seem to work as players in the differentiation process that drives breast cells to acquire distinct phenotypes related to a specific BC subtype.

Abstract Copy number alterations (CNAs) are a frequent feature in human breast cancer, and one of the hallmarks of genomic instability. The FOSL1, GSTP1 and CCND1 genes are located at 11q13, a cytoband commonly affected by CNA in breast cancer, with relevant function in progression and invasion. Our main goal was to analyze CNAs of these genes and determine their association with breast cancer subtypes. Seventy-three cases of invasive breast tumors [52 Luminal, 7 HER2+ and 14 triple negative (TNBC) subtypes] were analyzed by TaqMan assays. CNAs were observed for all genes, with gains more frequently observed. Gains of the FOSL1 gene were observed in 71% of the cases. This gene was the only one with a statistically significant difference (p<0.001) among tumor subtypes, with increased copy number in TNBC compared to luminal and HER2+. No significant association of CNA and clinical and histopathological parameters from the patients was observed. Additional studies in larger breast cancer patient cohorts based on more refined molecular subtypes are necessary to confirm the observed association of FOSL1 gain with aggressive breast tumors phenotypes.

Abstract MicroRNAs (miRNAs) play an essential role in gene expression and affect the development of tumours, including breast cancer (BC). Polymorphisms in miRNA genes can affect the interaction of miRNAs with their target messenger RNA by interfering, creating or disrupting target sites. The single nucleotide polymorphism (SNP) rs2910164, located in the seed region of miR146a, was shown to be associated with BC among different populations. In the present study, we investigated whether rs2910164 is associated with BC in 326 patients and 411 controls from a Brazilian population of predominantly European ancestry. The presence of the allele rs2910164*C was associated with an increased risk of BC (OR=1.4, 95% CI=1.03-1.85, p = 0.03). We also analysed publicly available RNA-seq data to evaluate if miR146a is differentially expressed in different subtypes of BC. Genotyping was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). By leveraging public data from TCGA database, we analysed 461 patients and found that miR146a is significantly more expressed in BC than in non-tumor tissue (1.47 fold, p = 0.02) and is expressed to a greater degree in aggressive BC subtypes.

O carcinoma bucal é o sexto tipo mais comum de câncer no mundo e o sétimo no Brasil, onde ocorre a maior incidência da América Latina. A sobrevida média de aproximadamente cinco anos permanece como uma das menores entre os principais cânceres, justificando estudos que auxiliem no delineamento de estratégias de prevenção. Este estudo objetivou avaliar em uma amostra de 91 pacientes portadores de carcinomas bucais características epidemiológicas; fatores de risco, clínicos e histopatológicos. A média de idade foi de 58,62 ± 10,46 anos e a razão sexual de 6,6:1,0 (79 homens e 12 mulheres). A etnia euro-descendente foi predominante com 79 (86,8%) pacientes. Oitenta e cinco (93,4%) indivíduos eram tabagistas e 70 (76,9%) etilistas. As localizações anatômicas prevalentes foram: 27 tumores (29,7%) de língua; 18 (19,8%) de assoalho; 11(12,1%) de orofaringe e 11 (12,1%) de mucosa. Cinqüenta e sete (62,6%) pacientes apresentaram os linfonodos comprometidos e três apresentaram (3,3%) metástases à distância. A maioria dos pacientes (43,2%) recebeu tratamento cirúrgico e radioterápico. Com exceção da proporção sexual, nossos dados concordam com os freqüentemente descritos para portadores de carcinomas bucais.

Oral carcinoma is the sixth most frequent type of cancer in the world and the seventh most common in Brazil (the country with the highest incidence in Latin America). Mean five-year survival remains one of the lowest among the main cancers, thus justifying studies that contribute to the development of preventive strategies. The aim of this study was to compare the epidemiological, clinical, and histological characteristics of 91 patients with oral carcinoma. Mean age was 58.62 ± 10.46 years, and male-to-female ratio was 6.6:1.0 (79 men and 12 women). European descendants predominated with 79 patients (86.8%). Eighty-five individuals (93.4%) smoked and 70 (76.9%) consumed alcohol regularly. Anatomical distribution of tumors was: 27 (29.7%) tongue; 18 (19.8%) floor of mouth; 11 (12.1%) oropharynx; and 11 (12.1%) oral mucosa. Fifty-seven patients (62.6%) presented lymph node involvement and three (3.3%) had distant metastases. Surgery and radiotherapy were used in 43.2% of patients. With the exception of the male/female ratio (which was higher), our data are consistent with previous studies on oral carcinoma patients.

O carcinoma bucal é o sexto tipo mais comum de câncer no mundo e o sétimo no Brasil, onde ocorre a maior incidência da América Latina. A sobrevida média de aproximadamente cinco anos permanece como uma das menores entre os principais cânceres, justificando estudos que auxiliem no delineamento de estratégias de prevenção. Este estudo objetivou avaliar em uma amostra de 91 pacientes portadores de carcinomas bucais características epidemiológicas; fatores de risco, clínicos e histopatológicos. A média de idade foi de 58,62 ± 10,46 anos e a razão sexual de 6,6:1,0 (79 homens e 12 mulheres). A etnia euro-descendente foi predominante com 79 (86,8%) pacientes. Oitenta e cinco (93,4%) indivíduos eram tabagistas e 70 (76,9%) etilistas. As localizações anatômicas prevalentes foram: 27 tumores (29,7%) de língua; 18 (19,8%) de assoalho; 11(12,1%) de orofaringe e 11 (12,1%) de mucosa. Cinqüenta e sete (62,6%) pacientes apresentaram os linfonodos comprometidos e três apresentaram (3,3%) metástases à distância. A maioria dos pacientes (43,2%) recebeu tratamento cirúrgico e radioterápico. Com exceção da proporção sexual, nossos dados concordam com os freqüentemente descritos para portadores de carcinomas bucais.

Oral carcinoma is the sixth most frequent type of cancer in the world and the seventh most common in Brazil (the country with the highest incidence in Latin America). Mean five-year survival remains one of the lowest among the main cancers, thus justifying studies that contribute to the development of preventive strategies. The aim of this study was to compare the epidemiological, clinical, and histological characteristics of 91 patients with oral carcinoma. Mean age was 58.62 ± 10.46 years, and male-to-female ratio was 6.6:1.0 (79 men and 12 women). European descendants predominated with 79 patients (86.8%). Eighty-five individuals (93.4%) smoked and 70 (76.9%) consumed alcohol regularly. Anatomical distribution of tumors was: 27 (29.7%) tongue; 18 (19.8%) floor of mouth; 11 (12.1%) oropharynx; and 11 (12.1%) oral mucosa. Fifty-seven patients (62.6%) presented lymph node involvement and three (3.3%) had distant metastases. Surgery and radiotherapy were used in 43.2% of patients. With the exception of the male/female ratio (which was higher), our data are consistent with previous studies on oral carcinoma patients.

Individual variability in xenobiotic metabolism has been associated with susceptibility to developing complex diseases. Genes involved in xenobiotic metabolism have been evaluated in association studies; the difficulty of obtaining accurate gene frequencies in mixed populations makes interpretation of the results difficult. We sought to estimate population parameters for the cytochrome P450 and glutathione S-transferase gene families, thus contributing to studies using these genes as markers. We describe the frequencies of six genes (CYP1A1, CYP2D6, CYP2E1, GSTM1, GSTT1, and GSTP1) and estimate population parameters in 115 Euro-descendants and 196 Afro-descendants from Curitiba, South of Brazil. PCR-based methods were used for genotyping, and statistical analysis were performed by AMOVA with ARLEQUIN software. The mutant allele frequencies in the Afro-descendants and Euro-descendants, respectively, were: CYP1A1*2A = 30.1% and 15.2%; CYP2D6*4 = 14.5% and 21.5%; CYP2E1*5B = 7.9% and 5%; GSTP1*B = 37.8% and 28.3%. The null genotype frequencies were: GSTM1*0 = 36.8% and 46.1%; GSTT1*0 = 24.2% and 17.4%.

The African descent population of the Bananal community in the Brazilian state of Bahia (BA) was characterized as a genetic isolate and analyzed for some short tandem repeat (STR) microsatellite autosomic polymorphic loci (CSF1PO, TH01, TPOX, F13A1, FESFPS and vWA). These genetic variants were further compared to data obtained from an urban sample from the town of Jequié (BA) regarding demographic and anthropogenetic aspects. The Bananal sample comprised 32 unrelated individuals whereas Jequié was represented by 76 individuals. The Bananal Negroid Phenotypic Index (NPI) was 0.98 and the Negroid Cultural Index (NCI) 0.24. Consanguineous marriages occurred at a frequency of 34.61% and the F value was 0.0126. All six loci studied were in Hardy-Weinberg Equilibrium (p > 0.05). The genotypic and allele frequencies of the CSF1PO and vWA loci were similar. In the Bananal population the genic diversity of the THO1 locus was 66.8% and that of the F13A1 locus was 83.7%. The estimated ethnic racial admixture was 81% African and 19% Amerindian. The multiple correlation coefficient (R²) indicated adequate adaptation (99%). Total genetic variation for the six loci was 82.9% with an index of 6.7% for population subdivision (G ST' = 0.067). Anthropologic data and results obtained from the allele frequencies of the loci studied are indicative of a genetic isolate in Bananal, reminiscent of the a 'quilombo community' (i.e. one founded by run away slaves).

Bone marrow cytogenetic studies were performed on 93 patients with primary myelodysplastic syndrome (MDS) diagnosed at the Clinical Hospital of the Federal University of Paraná, Brazil. Chromosomal alterations were observed in 69% of the patients. Monosomy of chromosome 7, deletions of 7q, 5q, 12p and 20q, rearrangements of 11q23 and trisomies of chromosomes 8 and 21 were the most frequent abnormalities observed. Among adult patients the most frequent aberrations were rearrangements of 11q23 and 12p deletions. In the pediatric group, 5q deletions and monosomy of chromosome 7 were the most common alterations.

Os animais silvestres têm sido utilizados como bioindicadores quando o ambiente é exposto a estressores químicos. Em geral, os agentes químicos podem induzir às alterações cromossômicas dos tipos falhas e quebras. Tayassu tajacu, é uma espécie aparentada dos porcos verdadeiro e apresenta uma grande estabilidade cariotípica. As únicas alterações descritas são em relação a forma do cromossomo X. Foram observadas falhas e quebras cromossômicas durante as análise citogenética. Estas alterações foram detectadas em cromossomos autossômicos. Levantamentos realizados na literatura associados as dados observados nos exemplares estudados, indicam um vermífugo, a base de ivermectina, como o possível causador dessas alterações cromossômicas.

Wild animals have been used as bioindicators in situations in which the environment was exposed to chemical agents. In general, chemical agents may induce chromosomal aberrations, such as breaks and gaps. The peccary, Tayassu tajacu is a pig relative that exhibits a very stable karyotype with the only described alterations being of the form of the X chromosome. Chromosomal gaps and breaks were observed at high frequencies during cytogenetics analyses. These alterations were observed in the chromosomes autossomics. Reviews of the literature and of the data described herein suggests that an vermifuge, the ivermectin base, was the most likely cause of these chromosomal alterations.