Made available in DSpace on 2014-06-12T15:53:53Z (GMT). No. of bitstreams: 2 arquivo5243_1.pdf: 854827 bytes, checksum: fb13a669eb1c6cefe0fff9ed7f1d9ffe (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2006 / O câncer de cólon uterino é apontado mundialmente como o mais incidente em mulheres, e o HPV tem sido descrito como o principal causador dessa patogenia. Durante o processo patogênico, o HPV interfere nos mecanismos gênicos da célula, daí a grande importância dos estudos desenvolvidos com a técnica de microarranjos que têm apresentado à comunidade científica diversos genes relacionados à infecção. Como os polimorfismos de base única (SNPs) vêm sendo associados a susceptibilidade ou não a doença, o presente trabalho descreve o programa SNP8, o qual foi desenvolvido para a análise de SNPs que possam ocorrer em regiões codificadoras (CDS) do genoma humano. O programa SNP8 é de livre acesso pela internet e requer apenas informações a respeito do gene que se pretende estudar, como nome, ID e símbolos oficiais. Em seguida o programa inicia a busca e alinha as seqüências RefSeq Exons, encontradas no banco público do NCBI (http://www.ncbi.nlm.nih.gov) e das ESTs, encontradas no banco público do UCSC Genome Browser (genome.ucsc.edu). Os SNPs encontrados entre essas seqüências são armazenados para posteriores análises. Em um processo passo, o programa busca as seqüências de SNPs já anotadas no banco público do NCBI e as compara com os SNPs previamente armazenados pelo programa. As comparações que coincidem são descartadas e as que não coincidem são propostas como potenciais novos SNPs, os quais são alinhados com a seqüência CDS do gene em estudo para a determinação da posição desses potenciais novos SNPs no CDS. Durante a validação do programa foram encontrados muitos potenciais novos SNPs em regiões CDS, dos quais 53,12% foram não sinônimos e 46,88% foram sinônimos. Esses SNPs foram confirmados por 30 70% do total de ESTs analisadas para cada gene. Com a descoberta desses potenciais novos SNPs para genes importantes relacionados a patogenia do HPV, nós sugerimos uma análise de confirmação desses potenciais SNPs encontrados pelo programa SNP8, o que acarretaria numa ampliação do banco dbSNP, de onde os dados foram retirados. Devido ao programa SNP8 trabalhar com dados atualizados dos bancos de dados do NCBI e do UCSC Genome Browser, a comunidade científica está melhor informada dos diferentes SNPs que podem ser encontrados exclusivamente em regiões CDS do genoma humano

Made available in DSpace on 2014-06-12T23:03:15Z (GMT). No. of bitstreams: 2 arquivo8794_1.pdf: 857147 bytes, checksum: 8e2d8e225ca76e04cb1b807a476b5487 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2003 / Evidências clínicas e epidemiológicas têm sugerido que a infecção genital causada pelo papilomavírus humano (HPV) pode ser generalizada e freqüentemente responsável por infecções clinicamente indetectáveis em outras mucosas. A colposcopia associada à citologia esfoliativa têm sido importantes métodos para detecção e diagnóstico das lesões pré-malignas e do câncer do colo uterino. Entretanto, o uso da colposcópio em cavidade oral (Oroscopia) para detecção de lesões incipientes na mucosa oral é ainda pouco estudado. O objetivo do presente estudo foi avaliar a eficácia da utilização do instrumento conhecido como colposcópio como meio auxiliar de diagnóstico das alterações epiteliais na mucosa oral em pacientes portadoras de lesões indicativas de infecção pelo HPV localizadas no colo uterino. Foram aleatoriamente selecionadas 50 pacientes portadoras de infecção por HPV em mucosa cervical provenientes do Serviço de Colposcopia do Hospital das Clínicas do Centro de Ciências da Saúde, Universidade Federal de Pernambuco. As pacientes foram submetidas à investigação da cavidade oral através de inspeção visual, oroscopia e citologia esfoliativa. As pacientes avaliadas tinham em média 33.5 anos de idade, variando de 19 a 50 anos. Do total, 24 tinham lesão intraepitelial escamosa de baixo grau e 26 de alto grau. As pacientes relataram em média terem tido 3,4 parceiros sexuais variando de 1 a 9 parceiros. Não foi observada nenhuma alteração na mucosa oral das pacientes avaliadas. O uso do colposcópio na cavidade oral (oroscopia) permite a visualização das mucosas labiais superior e inferior, mucosa jugal, língua, assoalho e palato duro, em seu terço médio. Houve limitações na observação da área tonsilar. Não foi encontrada associação entre lesão escamosa intra-epitelial cervical de baixo e alto grau e a idade, número de parceiros sexuais, idade da primeira relação sexual e prática de sexo oral

Head and neck cancers represent a group of tumors with two different etiologies. The first type is associated with the viral HPV infection, the second one is virus-independent and it is associated with smoking and alcohol consumption as two main risk factors. Numerous studies show that HPV-positive tumors are more frequent in younger patients, as well as that the prognosis and overall survival of these patients is remarkably better. Therefore, the modification of the treatment is considered. For this, however, specific, sensitive and clinically relevant biomarkers for accurate identification of tumor etiology is needed. Suitable candidates for such biomarkers are miRNAs, small non-coding regulatory molecules stable in archived samples, that have been shown as differentially expressed in human cancers and the expression pattern seems specific for tumors of different origin. The submitted thesis focuses on miRNA profiling in HPV-positive and HPV-negative tonsillar tumors and cervical carcinomas with the aim to find out the differences between regulation of important carcinogenetic pathways of tumors of viral and non-viral etiology. Our data have shown very large heterogeneity of the miRNA expression profiles of these tumors. Despite the well characterized and uniform samples collection, we have found...

acase@tulane.edu / This dissertation is an ethnographic study of the corruption narratives surrounding the quest for and the delivery of reproductive health care in contemporary Romania. Using as case study two public health campaigns targeting cervical cancer through early detection (Papanicolaou testing) and prevention (Human Papilloma Virus vaccination), it explores the ways Romanian women imagine the newly liberalized state and define themselves as post-Socialist citizens. The recent reforms in the provision of medical care have highlighted once again reproduction as a site of contestation. In sharp contrast with the Socialist pro-natalist policies, we currently witness the state’s progressive withdrawal from regulating reproduction, paralleled with the privatization of significant segments of reproductive health care delivery and with the marketization of women’s health. The range of reproductive choices has multiplied, but the emergence of new standards of inclusion/exclusion has limited the access to adequate care for many Romanian women. My interlocutors’ multi-layered discourses of reproduction and corruption are intrinsically ideological, revealing a folded blaming: of the former Socialist state paternalism and of the present post-Socialist state failure. In this context of unprecedented socio-cultural transformation, personhood becomes situational, shifting back and forth from Romanian citizen (when blaming the state for failing to provide proper reproductive assistance), to private person (when resisting mandatory national reproductive care programs). If we aim to decipher women’s responses to the Pap testing and HPV vaccination campaigns, we need to go beyond the ethnographically documented understandings of ‘risk, ’prevention,’ and ‘early detection.’ In a place such as present-day Romania, where bribe-offering is the idiom through which patients and doctors communicate, reproductive health care constitutes a privileged locus for analyzing how corruption discursively tames unsettled medical landscapes. By gathering the corruption narratives surrounding reproductive health care delivery, this dissertation grasps the micro-political factors that shape women’s local interactions, but it also analyzes the impact of “small scale” findings at a national and transnational level. My anthropological account – of what appears in retrospect to be “the chronicle of a failure foretold” – would be a crucial tool for policy makers in their future attempts to implement successful reproductive health programs. / 1 / Cristina A. Pop

No description available.

Cervical cancer is preceded by a spectrum of abnormalities in the cervical epithelium. Research supports an etiological role for certain types of human papillomaviruses (HPVs) in cervical pathology. More than 70 HPV genotypes have been characterized based on complete genome sequences and of these, about half infect the genital tract. Genital HPVs are further classified as either "high risk" or "low risk" types based on their association with cervical cancer. The demonstration that there is a relationship between HPV infection and cervical cancer has been dependent on a number of viral nucleic acid-based detection systems such as Southern blot and polymerase chain reaction. However, the lack of methods which discriminate between a specific HPV type and a large number of related HPV genotypes has made studies of disease association difficult. In the first part of this study, a recently developed Amplicor HPV Genotyping Kit was evaluated with respect to its ability to define HPV infection status. The L1 region was directly sequenced from the PCR product in 16 clinical samples to determine which genotype(s) was/were present. Sequencing data from one sample suggested a mixed infection and therefore the PCR product was cloned and sequenced to see if more than one genotype was present. Fifteen out of the sixteen samples sequenced were HPV genotypes which are not represented on the Amplicor Genotyping Kit test strips. The samples are rare HPV types (HPV 61, 62, CP6108 and CP8304). The second part of this study examined the issue of persistence and in particular, I have considered the issue of an appropriate definition of persistence. A number of patients who had evidence of HPV 16 or HPV 18, 6 and 66 were investigated using samples obtained on at least two occasions. Molecular variants of either the LCR gene for HPV 16 or the L1 gene for the other HPV types were studied. No differences in LCR or L1 gene sequence in sequential same patient samples were observed. Two HPV 16 LCR alleles were seen for six patients of which 8/10 showed one nucleotide change at base 7518 and 2/10 were identical to the prototype. Based on a compilation of published studies on HPV 16 variants and subtypes for the long control region, the number of HPV 16 LCR alleles, worldwide, was determined. One HPV 66 and two HPV 18 and HPV 6 L1 alleles were observed. When examining persistence, one must consider the frequency of specific variants (alleles) in the study population. A common variant detected over time could either be a persistent infection or a reinfection with the same viral variant. / Thesis / Master of Science (MS)

Infection with Human papillomaviruses has been suggested to play an important role in the etiology of a number of human malignancies. The most investigated of HPVs is HPV-16. Infection with HPV-16, in association with other unknown factors, is implicated in the development of cervical cancer. Genetic analysis of HPVs has been hampered by the lack of an in vitro system in which the complete replicative cycle and the transcription of the various genes is possible. Replication and transcription of HPVs seem to be in part regulated by cellular factors expressed at different stages in the maturation of epithelial cells which constitute the normal hosts of those viruses. This study was primarily designed to address this difficulty. HPV-16 genome was introduced into a viral system, HSV-1, hoping that virally encoded factors can substitute for cellular factors required for the expression of HPV genes. This hypothesis was tested by analyzing the activity of the HPV-16 early promoter P₉₇ , in the constructed recombinant, in cells which are unsusceptible to infection with HPV-16. In Vero cells infected with the recombinant, P₉₇ was shown to be active. This suggests that HSV-1 encoded factors can influence transcription from endogenous papilloma promoters. / Thesis / Master of Science (MS)

O câncer de cervical é causado por uma infecção persistente por algum dos tipos oncogênicos de Papilomavírus Humano (HPV) e continua a ser um problema de saúde pública, especialmente nos países em desenvolvimento. Por Peptide Phage Display, foram selecionadas sequências de peptídeos com afinidade de ligação a linhagens celulares ou a tumores associados ao HPV. Dentre elas, foi possível identificar sequências contidas em moléculas importantes para a progressão de tumores, como a -manosidase e triptase, enzimas que desempenham um papel importante na progressão tumoral. Para caracterizar o efeito da inibição de -manosidase II na terapia de tumores cervicais em camundongos, utilizamos a droga Swainsonina (SW), previamente descrita como inibidor desta enzima. Nós testamos o efeito desta droga tratando animais inoculados com células tumorais que expressam os oncogenes E6 e E7 de HPV16. Observamos que os animais tratados com Swainsonina apresentaram crescimento tumoral significativamente mais rápido do que os animais controle. Investigando os mecanismos por trás desse efeito, descobrimos que embora SW module parcialmente os macrófagos associados aos tumores, o tratamento induz o acúmulo de células com fenótipo mieloderivado supressor no baço dos animais, potencializando o efeito tolerogênico dos tumores sobre o sistema imune. Sendo assim, sugerimos cautela no uso deste fármaco para a terapia de pacientes com tumores HPV&#43. Outro braço do trabalho foi avaliar o papel da triptase, que é produzida por mastócitos, no infiltrado inflamatório. Para isto padronizamos um modelo de co-cultura de esferóides tumorais da linhagem TC-1 com a linhagem de mastócitos murinos PT18. Através deste modelo pudemos observar que a linhagem tumoral consegue induzir a desgranulação dos mastócitos independentemente de anticorpos. Além disso, quando em co-cultura, a linhagem tumoral parece estar aumentando a meia-vida dos mastócitos e estimulando a proliferação destes. Em experimentos in vivo observamos que tumores induzidos com as células PT18 e TC-1 cresceram mais rapidamente do que tumores induzidos apenas com TC-1. Através da imunofenotipagem dos tumores ficou evidenciado um aumento de células CD31+ e no infiltrado inflamatório total de tumores induzidos com o co-cultivo. Justificando o fato destes crescerem mais rapidamente, sugerindo que os mastócitos podem ter efeitos tanto proliferativos quanto no processo de angiogênese tumoral. / Cervical cancer is caused by a persistent infection by some of the oncogenic types of Human Papillomavirus (HPV) and continues to be a public health problem, especially in developing countries. By Peptide Phage Display peptide sequences were selected with binding affinity to cell lines or to HPV-associated tumors. Among them, it was possible to identify sequences contained in molecules important for the progression of tumors, such as -mannosidase and tryptase, enzymes that play an important role in tumor progression. To characterize the effect of -mannosidase II inhibition on cervical tumor therapy in mice, we used the drug Swainsonina (SW), previously described as an inhibitor of this enzyme. We tested the effect of this drug by treating animals inoculated with tumor cells expressing HPV16 E6 and E7 oncogenes. We observed that Swainsonine treated animals had significantly faster tumor growth than control animals. Investigating the mechanisms behind this effect, we found that although SW partially modulates tumor-associated macrophages, the treatment induces the accumulation of cells with suppressive myeloderivative phenotype in the animals spleens, enhancing the tolerogenic effect of tumors on the immune system. Therefore, we suggest caution in the use of this drug for the therapy of patients with HPV&#43 tumors. Another arm of the study was to evaluate the role of tryptase, which is produced by mast cells, in the inflammatory infiltrate. For this we standardized a co-culture model of tumor spheroids of the TC-1 lineage with the murine mast cell line PT18. Through this model we could observe that the tumoral lineage can induce mast cell degranulation independently of antibodies. In addition, when co-cultured, the tumoral lineage appears to be increasing the half-life of mast cells and stimulating the proliferation of these. In in vivo experiments we observed that tumors induced with PT18 and TC-1 cells grew faster than tumors induced only with TC-1. Tumor immunophenotyping revealed an increase in CD31&#43 cells and in the total inflammatory infiltrate of tumors induced with co-culture. Justifying the fact that they grow faster, suggesting that mast cells can have both proliferative effects and the process of tumor angiogenesis.

BACKGROUND: Now considered a cornerstone of healthcare, patient-provider communication has long been studied and analyzed. Medical associations such as the Joint Commission and the American Association of Orthopaedic Surgeons (AAOS) have strongly endorsed for physicians to exercise patient-focused communication, a practice that involves showing empathy, involving patients in medical care decisions, eliciting concerns, and educating patients on treatment options (Joint Commission, 2016; AAOS, 2017). A lack of patient-provider communication has previously been identified as a significant factor in adverse medical outcomes occurring within hospitals (Khan et al., 2017). Bridging the communication disparity between patients and providers is crucial to improving overall patient outcome. Primary care providers are especially essential to improving overall patient outcome because they serve as the first point of contact for many patients accessing the healthcare system. While there is much literature on the importance of effective patient-provider communication, few studies provide technology-based tools that can enhance this establishment of communication. Human Papillomavirus is presently the most common sexually transmitted infection (STI) nationwide with 79 million Americans currently infected (CDC, 2017). Approximately 42,700 HPV-attributable cancers are diagnosed in the United States annually, and HPV is believed to be responsible for over 90% of cervical cancer cases (CDC, 2018). The Advisory Committee on Immunization Practices (ACIP) currently recommends three preventative HPV vaccines. Despite high rates of infection, HPV vaccination rates nationwide remain low as coverage of the HPV vaccine falls behind that of coverage for required vaccines like the tetanus, diphtheria, and acellular pertussis vaccine (Tdap) (Reagan-Steiner, 2016). Previous studies have sought to address factors that affect decisions to vaccinate children. An analyzation of the National Immunization Survey of Teens has identified that parents’ belief that the HPV was not necessary as a main factor (Darden et al., 2013). As a result, there is a gap needed to be filled by providers to educate parents on the importance of the HPV vaccine. PURPOSE: The current study sought to determine the effectiveness of a web-based mobile health education program called Wheel of Wellness (WoW) on patient-provider communication, to assess the viability and impact of WoW to increase HPV vaccination rates in age eligible children (boys and girls aged 9-17) and to augment awareness about the benefits of HPV vaccination in both these children and their guardians. RESEARCH METHOD AND DESIGN: As of August 2018, twenty-seven parents of children between the ages of 9 and 17 years of age within the Pediatrics and Adolescent departments of Boston Medical Center (BMC) have been recruited. Parents enrolled in the WoW program to compile a list of concerns to be shown to a provider during their child’s appointment. Participants were asked questions to determine initial knowledge on the HPV vaccine, and their opinions on the HPV vaccine. Following their appointment, participants completed a questionnaire to assess opinions on the WoW program in facilitating communication with their provider on the HPV vaccine and related cancers. Seven physicians were interviewed to assess their views on the WoW program in facilitating communication with their patients on the HPV vaccine and related cancers. RESULTS: Initial stages of this study found that views on the effectiveness of the WoW program in facilitating patient and provider communication on the different aspects of HPV vaccination and affecting parents’ decisions to vaccinate their children were mixed by both patients and their providers. Based on the WoW feedback collected from parents, the system was widely acceptable in terms of ease in usage and with the majority of parents (92%) reporting that the WoW website is helpful for communicating their health concerns with their provider. However, the majority of providers reported having never been presented the WoW system and expressed views that WoW was inefficient as it was a parallel system to existing workflow. This study determined that of the 12 participants who had one dose of the vaccine prior to enrollment, 75% of these participants completed the HPV vaccine series during the study. CONCLUSION: Based on the initiation and completion statistics reported, this shows great potential for the use of the BNI coupled with the WoW system to help improve rates of initiation and completion of HPV vaccination going forward as the intervention may have helped encourage parents to either initiate vaccination or complete their child’s previously started series. Further studies should explore ways of empowering patients to facilitate more communication with their providers and improvements to technology to enhance provider recommendation in order to promote an increase in HPV vaccine completion. / 2021-06-17T00:00:00Z

O desenvolvimento de metodologias sobre integração de dados na área de biologia de sistemas é de grande importância devido ao aumento contínuo de dados resultantes de análises globais que são depositados em bancos de dados públicos. Poucas metodologias e ferramentas de bioinformática levam em consideração a diferenciação entre drivers e passengers, fundamental para a identificação de genes importantes para o desenvolvimento e progressão tumoral. Os perfis de expressão gênica têm possibilitado a identificação de assinaturas genéticas em uma grande variedade de tumores humanos. Além disso, as alterações epigenéticas, como a expressão de microRNAs (miRNA) e a metilação do DNA, também contribuem para o desenvolvimento de diversos tipos de doenças. Entretanto, a grande maioria destes estudos não mostra integração dos resultados obtidos pelas diferentes estratégias utilizadas, o que teria maior impacto na identificação de drivers moleculares. Neste estudo foi realizada a integração de quatro níveis de alterações em 31 amostras de câncer de pênis (CaPe): alteração do número de cópias do DNA, metilação de ilhas CpGs, expressão de miRNAs e expressão de transcritos codificadores. O conhecimento das alterações genéticas e epigenéticas relacionadas ao desenvolvimento de câncer de pênis é bastante limitado, devido principalmente a sua rara incidência. Uma parcela significativa dos casos de CaPe tem sido associada com a infecção pelo Papilomavírus Humano (HPV). A metodologia para integração de dados foi aplicada utilizando duas abordagens: (1) estudo das alterações em câncer de pênis (tumor e normal) independente da infecção pelo HPV e (2) estudo das alterações relacionadas à infecção pelo HPV. A análise foi dividida em duas etapas, com a seleção de genes alvos específicos da doença e inferência de módulos a partir desses alvos. Destacam-se na metodologia a seleção de genes candidatos a driver utilizando a atribuição de pesos para cada alteração seguindo critérios pré-determinados, e.g. se o gene estava presente em uma região rara, após classificação pelo DGV (Database of Genomic Variants) e a utilização desses genes como alvos para identificação das possíveis relações entre eles e os módulos. Também foi realizada a adaptação da metodologia de redes em módulos, com a inclusão de genes passengers e interação proteína-proteína (PPI) como um critério para seleção dos módulos. Essa análise se mostrou eficaz na identificação de módulos gênicos bem relacionados com os drivers, resultando na escolha de vias biológicas potencialmente responsáveis pelo desenvolvimento do tumor. Os genes identificados após a comparação entre amostras tumorais e normais (SOX17, TWIST1, CAV1, PPARG, FLI1 e TNFSF10) e no estudo entre amostras positivas e negativas para infecção pelo HPV (PCNA, SOX14 e RFC4) foram validados in situ por técnicas independentes. Para validação in silico das alterações encontradas na metodologia de integração de dados e para validação da metodologia de redes em módulos foram utilizadas 255 amostras de glioblastoma multiforme obtidas no banco de dados TCGA (The Cancer Genome Atlas). Foram identificadas vias biológicas importantes relacionadas ao processo tumoral, como regulação do crescimento celular (GO:0001558, p=0,0062), homeostase (GO:0048872, $p=0,0082) e regulação da transcrição (GO:0003700, p=0,00089). Também foi realizada uma meta-análise utilizando amostras do TCGA, que encontrou um perfil similar de expressão para os genes CAV1, DLC1,FLI1, MSX1, NRN1, PML, PPARG e SOX17 (T vs N) e PCNA e RFC4 (HPV+ vs HPV-). Para o nosso conhecimento, esse é o primeiro estudo em CaPe utilizando análise integrada de quatro níveis de alteração. Além disso, foram encontradas alterações não randômicas capazes de modificar transcritos específicos e contribuir para o conhecimento da patobiologia dos tumores de pênis. / Methodologies for data integration in systems biology area have great importance due to continuous increase of public data resulting from large-scale analysis, which are deposited in public databases. Few methodologies and bioinformatics tools take into consideration the differentiation between drivers and passengers, fundamental for the identification of important genes for tumor development and progression. The gene expression profiles have allowed the identification of genetic signatures in a wide variety of human tumors. In addition, epigenetic changes, such as the expression of microRNA (miRNA) and DNA methylation, also contribute to the development of a veriety of diseases. However, most of these studies did not show integration of results obtained by different strategies used, which would have increased impact to identify molecular drivers. This study provides a methodology for integration of four levels of changes in 31 samples of penile cancer (PeCa): copy number alterations, DNA methylation of CpG islands, miRNA expression and gene expression of coding transcripts. Knowledge about genetic and epigenetic changes related to the development of penile cancer is very limited, mainly due to its rare incidence. A significant portion of PeCa samples has been associated with infection by Human papillomavirus (HPV). The methodology for integrative data was applied using two approaches: (1) the study considering alterations in penile carcinoma (tumor and normal), independent of HPV infection and (2) the study considering alteration related to HPV infection in PeCa. In each study, the methodology was divided into two stages, with the selection of target genes and the inference of disease specific modules from these targets. It is highlighted in the methodology the selection of candidate genes using the driver assigning weights to each change following predetermined criteria, e.g if the gene was present in a rare region after classification using the DGV database (Database of Genomic Variants) and the use of these genes as seeds for identification of possible relationships between them and the modules. For this, another contribution of this study was the adaptation of module network methodology, with the inclusion of passengers genes and protein-protein interaction (PPI) as a criteria to select the modules. This analysis was effective in identifying gene modules and related drivers, resulting in the choice of biological pathway potentially responsible for the tumor development. The genes identified after comparing tumor and normal samples (SOX17, TWIST1, CAV1, PPARG, FLI1 and TNFSF10) and the genes identified in the study of positive and negative samples for HPV infection (PCNA, SOX14 and RFC4) were validated in situ by independent techniques. For in silico validation of the changes found in the integrative methodology and the modules network were used 255 samples of glioblastoma multiforme obtained at TCGA database (The Cancer Genome Atlas). Biological pathways have been identified related to the tumoral process, such as cell growth regulation (GO:0001558, p=0,0062), homeostasis (GO:0048872, p=0,0082) and transcription regulation (GO:0003700, p=0,00089). Also, a meta-analysis was performed using samples from TCGA, who found a similar expression profile for CAV1, DLC1, FLI1, MSX1, NRN1, PML, PPARG and SOX17 (T vs N) and PCNA and RFC4 genes (HPV + vs HPV-). To our knowledge, this is the first integrative analysis in PeCa using a four-level of gene alterations. In addition, it was found non-random alterations capable to modifying specific transcripts and contribute to the knowledge about the pathobiology of penile tumors.