Thesis (M.S.)--University of Missouri-Columbia, 2005. / "May 2005" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 69-76).

Orientador: Carmen Silvia Bertuzzo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T19:05:10Z (GMT). No. of bitstreams: 1 Rossanese_LillianBarbosadeQueiroz_D.pdf: 6549748 bytes, checksum: 054df2cab96a347008ff6d310b9dcfa9 (MD5) Previous issue date: 2012 / Resumo: Mutações germinativas no gene APC (Polipose adenomatosa coli) são responsáveis pela ocorrência de polipose adenomatosa familiar (PAF). Mutações somáticas levam à transformação maligna de adenomas. O objetivo desse trabalho foi identificar mutações germinativas no gene APC. No presente estudo, 20 pacientes com PAF foram estudados. A determinação das mutações germinativas no APC foi realizada por meio de sequenciamento, e as mutações foram comparadas com marcadores clínicos (sexo, idade no momento do diagnóstico, tabagismo, estádio TNM, classificação Coller-Astler e o grau de diferenciação do adenocarcinoma). Os dados foram comparados por meio do programa SPSS , com o teste de Fisher e teste de ?2 , considerando ? = 0,05. De acordo com os principais resultados da nossa amostra, 16 alelos com mutações deletérias (80 % dos pacientes) foram identificados, enquanto 7 (35%) pacientes não tinham mutações deletérias. Houve um predomínio de mutações nonsense (45% dos pacientes) e de mutações frameshift (20% dos pacientes). Não houve significância estatística entre as mutações germinativas identificadas e as variáveis clínicas consideradas em nosso estudo. Apenas a fase TNM foi associada com a presença de mutações deletérias. Os portadores com mutações deletérias tinha uma OR , 0,086 ( IC = 0,001-0,984 ); TNM I + II em comparação com III + IV , quando comparado com os pacientes sem mutações deletérias identificados. Neste estudo, demonstramos a heterogeneidade molecular de mutações germinativas no APC em portadores de PAF e a dificuldade para realizar diagnóstico molecular em uma população brasileira / Abstract: Adenomatous polyposis coli (APC) germline mutations are responsible for the occurrence of familial adenomatous polyposis (FAP). Somatic mutations lead to malignant transformation of adenomas. In this context, considering the significance of APC germline mutations in FAP, we aimed to identify APC germline mutations. In the present study, 20 FAP patients were enrolled. The determination of APC germline mutations was performed using sequencing, and the mutations were compared with clinical markers (gender, age at diagnosis, smoking habits, TNM stage, Astler-Coller stage, degree of differentiation of adenocarcinoma). The data were compared using the SPSS program, with the Fisher's exact test and ?2 test, considering ?=0.05. According to the main results in our sample, 16 alleles with deleterious mutations (80% of the patients) were identified while 7 (35%) patients had no deleterious mutations. There was a predominance of nonsense (45% of the patients) and frameshift (20% of the patients) mutations. There was no statistical significance between the APC germline mutations identified and the clinical variables considered in our study. Only TNM stage was associated with the presence of deleterious mutations. Patients with deleterious mutations had an OR, 0.086 (IC=0.001-0.984); TNM stage I + II in comparison with III + IV, when compared with the patients with no deleterious mutations identified. In this context, as a conclusion, we demonstrated the molecular heterogeneity of APC germline mutations in FAP and the difficulty to perform molecular diagnostics in a Brazilian population, considering the admixed population analyzed / Doutorado / Clinica Medica / Doutora em Ciências

No description available.

In the first part of this thesis, two chromosome Y specific genes ( SRYand TSPY) were chosen as the molecular targets to investigate the characteristics of fetal-specific DNA fragments in maternal plasma. By employing the touch down ligation-mediated PCR coupled with cloning and sequencing, the end property and the fragment species of fetal DNA were studied. / Noninvasive prenatal detection of fetal chromosomal aneuploidies is a much sought-after goal in fetomaternal medicine. The discovery of fetal DNA in the plasma of pregnant women has offered new opportunities for this purpose. However, the fact that fetal DNA amounts to just a minor fraction of all DNA in maternal plasma makes it challenging for locus-specific DNA assays to detect the small increase in sequences derived from a trisomic chromosome. On the other hand, although the clinical applications of plasma DNA for prenatal diagnosis are expanding rapidly, the biological properties of circulating DNA in plasma remain unclear. Recently, next-generation sequencing technologies have transformed the landscape of biomedical research through the ultra-high-throughput sequence information generated in a single run. Massively parallel sequencing allows us to study plasma DNA at an unprecedented resolution and also precisely detect fetal chromosomal aneuploidies in a locus-independent way. / Our group has demonstrated the use of massively parallel sequencing to quantify maternal plasma DNA sequences for the noninvasive prenatal detection of fetal trisomy 21. In the second part of this thesis, the clinical utility of this new sequencing approach was extended to the prenatal detection of fetal trisomy 18 and 13. A region-selection method was developed to minimize the effects of GC content on the diagnostic sensitivity and precision for the prenatal diagnosis of trisomy 13. To facilitate the next-generation sequencing-based maternal plasma DNA analysis for clinical implementation, two measures, i.e., lowering the starting volume of maternal plasma and barcoding multiple maternal plasma samples, were investigated. / Taken together, the results presented in this thesis have demonstrated the clinical utility of massively parallel sequencing of maternal plasma DNA and have also provided us a better understanding of the biology of circulating DNA molecules. / The third part of this thesis focuses on the massively parallel paired-end sequencing of plasma DNA. By analyzing millions of sequenced DNA fragments, the biological properties of maternal plasma DNA were elucidated, such as the size distribution of fetal-derived and maternally-contributed DNA molecules and the potential effect of epigenetic modification on DNA fragmentation. Moreover, the plasma DNA from hematopoietic stem cell transplant patients was characterized by paired-end sequencing approach. These sequencing data not only confirmed the predominant hematopoietic origin of cell-free DNA but also revealed the size difference between hematologically-derived and other tissue-derived DNA molecules in plasma. / Zheng, Wenli. / Adviser: Lo Yu Ming Dennis. / Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 261-275). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Lau, Wai Hung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 141-153). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

by Peter, Wei Gong Chang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 103-124). / ACKNOWLEDGEMENTS --- p.i / ABSTRACT --- p.ii / TABLE OF CONTENTS --- p.iv / ABBREVIATIONS --- p.viii / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- General introduction --- p.1 / Chapter 1.2 --- Human genome project --- p.5 / Chapter 1.3 --- Human adult heart cDNA library --- p.7 / Chapter 1.4 --- Human fetal heart cDNA library --- p.8 / Chapter 1.5 --- Sequencing of a human heart cDNA clone --- p.9 / Chapter 1.6 --- Knowledge of the role of selenium --- p.13 / Chapter 1.7 --- Mouse 56kDa selenium binding protein and acetaminophen-binding protein --- p.16 / Chapter CHAPTER 2 --- MATERIALS AND METHODS / Chapter 2.1 --- Plating out the cDNA library --- p.20 / Chapter 2.1.1 --- "Mediums, buffers and solutions" --- p.20 / Chapter 2.1.2 --- Bacteriophage clones preparation --- p.21 / Chapter 2.2 --- cDNA clone amplification by PCR --- p.23 / Chapter 2.3 --- Cycle sequencing of PCR products --- p.25 / Chapter 2.3.1 --- "Media, buffers and solutions" --- p.25 / Chapter 2.3.2 --- Preparation of sequencing reaction --- p.25 / Chapter 2.4 --- Gel electrophoresis using an automated A.L.F sequencer --- p.27 / Chapter 2.5 --- DNA sequence analysis --- p.29 / Chapter 2.6 --- Preparation of competent E. coli for transformation --- p.30 / Chapter 2.7 --- Transformation of plasmid into competent E. coll --- p.31 / Chapter 2.8 --- Mini-preparation of plasmid DNA --- p.32 / Chapter 2.9 --- Large scale plasmid DNA preparation by QIAGEN --- p.34 / Chapter 2.10 --- Cloning the human 56 kDa selenium binding protein (hSP56) into the pAED4 vector --- p.36 / Chapter 2.10.1 --- Bacterial strains and vector --- p.36 / Chapter 2.10.2 --- "Media, buffers and solutions" --- p.38 / Chapter 2.10.3 --- Primers design and PCR --- p.42 / Chapter 2.10.4 --- Purification of PCR products by Geneclean --- p.43 / Chapter 2.10.5 --- Restriction digestion of purified PCR product and pAED4 --- p.44 / Chapter 2.10.6 --- Ligation and transformation of hSP56 --- p.45 / Chapter 2.10.7 --- Screening and purification ofpAED4hSP56. --- p.47 / Chapter 2.11 --- Expression of hsp56 --- p.50 / Chapter 2.11.1 --- Induction of hSP56 expression --- p.50 / Chapter 2.11.2 --- SDS-PAGE and protein detection --- p.51 / Chapter 2.12 --- Northern hybriddization of hSP56 --- p.53 / Chapter 2.12.1 --- Animals & human tissue --- p.53 / Chapter 2.12.2 --- "Mediums, buffers and solutions" --- p.53 / Chapter 2.12.3 --- Preparation of total RNA --- p.56 / Chapter 2.12.4 --- Formaldehyde agarose gel electrophoresis --- p.57 / Chapter 2.12.5 --- Preparation of radioactive probe --- p.58 / Chapter 2.12.6 --- RNA transfer and Northern hybridization --- p.59 / Chapter 2.13 --- Chromosomal mapping of the hSP56 gene --- p.62 / Chapter CHAPTER 3 --- RESULTS / Chapter 3.1 --- The sequencing results of 553 cDNA clones --- p.63 / Chapter 3.2 --- Catalogues of genes expressed --- p.65 / Chapter 3.3 --- Sequence analysis of hSP56 --- p.71 / Chapter 3.4 --- Northern hybridization of hSP56 --- p.84 / Chapter 3.5 --- Cloning of hSP56 into pAED4 --- p.87 / Chapter 3.6 --- Expression of the hSP56 in E. coli --- p.89 / Chapter 3.7 --- Chromosomal mapping of the hSP56 gene --- p.92 / Chapter CHAPTER 4 --- DISCUSSION / Chapter 4.1 --- General discussion --- p.94 / Chapter 4.2 --- The possible roles of hSP56 and mSP56 --- p.101 / Chapter 4.3 --- Future prospects --- p.102 / REFERENCES --- p.103 / APPENDIX 1 --- p.125 / APPENDIX.2 --- p.127

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 5 uppsatser.

Approximate pattern matching problem is, given a reference sequence T, a pattern (query) Q, and a maximum allowed error e, to find all the substrings in the reference, such that the edit distance between the substrings and the pattern is smaller than or equal to the maximum allowed error. Though it is a well-studied problem in Computer Science, it gains a resurrection in Bioinformatics in recent years, largely due to the emergence of the next-generation high-throughput sequencing technologies. This thesis contributes in a novel generalized pattern matching framework, and applies it to solve pattern matching problems in general and alternative splicing detection (AS) in particular. AS is to map a large amount of next-generation sequencing short reads data to a reference human genome, which is the first and an important step in analyzing the sequenced data for further Biological analysis. The four parts of my research are as follows. / In the first part of my research work, we propose a novel deterministic pattern matching algorithm which applies Agrep, a well-known bit-parallel matching algorithm, to a truncated suffix array. Due to the linear cost of Agrep, the cost of our approach is linear to the number of characters processed in the truncated suffix array. We analyze the matching cost theoretically, and .obtain empirical costs from experiments. We carry out experiments using both synthetic and real DNA sequence data (queries) and search them in Chromosome-X of a reference human genome. The experimental results show that our approach achieves a speed-up of several magnitudes over standard Agrep algorithm. / In the fourth part, we focus on the seeding strategies for alternative splicing detection. We review the history of seeding-and-extending (SAE), and assess both theoretically and empirically the seeding strategies adopted in existing splicing detection tools, including Bowtie's heuristic and ABMapper's exact seedings, against the novel complementary quad-seeding strategy we proposed and the corresponding novel splice detection tool called CS4splice, which can handle inexact seeding (with errors) and all 3 types of errors including mismatch (substitution), insertion, and deletion. We carry out experiments using short reads (queries) of length 105bp comprised of several data sets consisting of various levels of errors, and align them back to a reference human genome (hg18). On average, CS4splice can align 88. 44% (recall rate) of 427,786 short reads perfectly back to the reference; while the other existing tools achieve much smaller recall rates: SpliceMap 48.72%, MapSplice 58.41%, and ABMapper 51.39%. The accuracies of CS4splice are also the highest or very close to the highest in all the experiments carried out. But due to the complementary quad-seeding that CS4splice use, it takes more computational resources, about twice (or more) of the other alternative splicing detection tools, which we think is practicable and worthy. / In the second part, we define a novel generalized pattern (query) and a framework of generalized pattern matching, for which we propose a heuristic matching algorithm. Simply speaking, a generalized pattern is Q 1G1Q2 ... Qc--1Gc--1 Qc, which consists of several substrings Q i and gaps Gi occurring in-between two substrings. The prototypes of the generalized pattern come from several real Biological problems that can all be modeled as generalized pattern matching problems. Based on a well-known seeding-and-extending heuristic, we propose a dual-seeding strategy, with which we solve the matching problem effectively and efficiently. We also develop a specialized matching tool called Gpattern-match. We carry out experiments using 10,000 generalized patterns and search them in a reference human genome (hg18). Over 98.74% of them can be recovered from the reference. It takes 1--2 seconds on average to recover a pattern, and memory peak goes to a little bit more than 1G. / In the third part, a natural extension of the second part, we model a real biological problem, alternative splicing detection, into a generalized pattern matching problem, and solve it using a proposed bi-directional seeding-and-extending algorithm. Different from all the other tools which depend on third-party tools, our mapping tool, ABMapper, is not only stand-alone but performs unbiased alignments. We carry out experiments using 427,786 real next-generation sequencing short reads data (queries) and align them back to a reference human genome (hg18). ABMapper achieves 98.92% accuracy and 98.17% recall rate, and is much better than the other state-of-the-art tools: SpliceMap achieves 94.28% accuracy and 78.13% recall rate;while TopHat 88.99% accuracy and 76.33% recall rate. When the seed length is set to 12 in ABMapper, the whole searching and alignment process takes about 20 minutes, and memory peak goes to a little bit more than 2G. / Ni, Bing. / Adviser: Kwong-Sak Leung. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical referencesTexture mapping (leaves 151-161). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

As maiores taxas de incidência de câncer de mama ocorrem em mulheres idosas, que apresentam tumores com expressão de receptores de estrógeno e/ou progesterona, de baixo estadiamento e menor taxa de proliferação, se comparado com as jovens. Um dos fatores de predisposição ao câncer de mama é mutação germinativa nos genes BRCA1 ou BRCA2, que podem compreender entre 5-10% das pacientes diagnosticadas. A grande maioria dos casos são ditos esporádicos, em que não há como estabelecer um único fator determinante. Dentre o escopo de possíveis causas estão as mutações somáticas, acumuladas no tecido mamário ao longo da vida. A identificação destas mutações permite melhor compreensão da carcinogênese e possibilita a criação de tratamentos cada vez mais personalizados. O gene PIK3CA, por exemplo, já está determinado como driver (responsáveis pela obtenção de vantagem seletiva de um determinado clone) para câncer de mama. As mutações patogênicas que ocorrem neste gene levam a ativação da via de Akt/mTOR, entre outras, que mantém o ciclo celular ativo. Um gene que vem sendo estudado recentemente é o PRKD1, cujas funções parecem estar ligadas à manutenção do fenótipo epitelial das células do tecido mamário. Assim, o objetivo desse trabalho identificar mutações germinativas nos genes BRCA1 e BRCA2, analisando também o histórico familiar para câncer de mama/ovário/próstata, e mutações somáticas no gene PRKD1 em pacientes pós menopausadas,. Foram incluídas quarenta e nove pacientes diagnosticadas com carcinoma ductal invasivo em idade superior a 54 anos, que preenchessem critérios da NCCN (National Comprehensive Cancer Network) para Síndrome de Câncer de Mama e/ou Ovário Hereditário e tinham disponível um fragmento tumoral emblocado em parafina coletado na ausência de tratamento neo adjuvante. A extração de DNA foi realizada a partir do sangue periférico para sequenciamento de BRCA1 e BRCA2, realizado através da plataforma Ion Torrent(TM) ou pelo método de Sanger. Os resultados obtidos por Ion Torrent(TM) foram analisados, primeiramente, através da ferramenta online Ion Reporter e os de Sanger através do programa Mutation Surveyor v.3.20. Para a caractetização das variantes encontradas foram utilizados: os bancos de dados BIC, LOVD, LOVD-IARC, UMD e ClinVar além dos preditores in silico da conservação dos aminoácidos entre as espécies Polyphen-2, SIF, Provean e AlignGVGD e do preditor de efeito no splicing HSF e bancos de dados de frequência alélica ExAC, 1000 genomas e NHLBI GO Exome Sequencing Project, seguindo os critérios da American College of Medical Genetics and Genomics em conjunto com a Association for Molecular Pathology. Para caracterização de mutação somática do gene PRKD1 determinou-se duas regiões de maior importância para serem sequenciadas: Ser738/Ser742 e Ser910 que fosforilam o domínio quinase da proteína, ativando-o. Vinte e três amostras tumorais tiveram DNA extraído. Também foi realizada uma análise das informações sobre PRKD1 do banco de dados COSMIC (Catalogue of Somatic Mutations in Cancer) e a construção de curvas de sobrevida (Kaplan-Meier) da expressão de PRKD1 utilizando a ferramenta online KM Plotter. A idade mediana das pacientes foi de 62 anos ao diagnóstico e de 64 anos na época de inclusão no estudo. A maioria tinha tumores de grau histológico II (63,27%), estádio clinico II (20%) e do subtipo luminal B (53,06%). Trinta e duas relataram parentes de primeiro grau afetados com câncer de mama/ovário/ próstata. Trinta e oito pacientes tiveram sequenciamento completo de BRCA1 e BRCA2 por Ion Torrent(TM) e onze tiveram sequenciamento parcial de BRCA1 e BRCA2 por Sanger. Variantes patogênicas foram encontradas em quatro pacientes (BRCA1=2/BRCA2=2). Uma nova variante missense foi identificada em BRCA2: c.3371A > G (p.Q1124R). Para o sequenciamento de PRKD1 quinze foram sequenciadas para Ser910 e de oito foi possível analisar o resultado. Nenhuma variante patogênica foi encontrada. Os dados obtidos sobre PRKD1 no COSMIC foram: de 2773 amostras, em apenas 15 (0,54%) foram identificadas mutações em PRKD1, 46% (7/15) provém de mulheres com idade superior a 55 anos e subtipo molecular Luminal. PRKD1 apresenta maiores frequência de mutação em câncer de intestino grosso (4,22%) e pele (4,02%). As curvas de sobrevida construídas no KM Plotter demonstram a alta expressão do gene parece ter impacto positivo na sobrevida das pacientes. Apesar da baixa frequência de mutações no PRKD1 este gene, outros dados demonstram que parece ter um papel de gene supressor de tumor no câncer de mama, que deve ser inibido de através de outros mecanismos como metilaçao de DNA / The highest rates of breast cancer incidence occur in elderly women, who present estrogen and / or progesterone receptor tumors, with a low clinical staging and lower proliferation rate compared to the young women. One of the factors predisposing to breast cancer is germline mutation in the BRCA1 or BRCA2 genes, which may comprise between 5-10% of the diagnosed patients. The vast majority of cases are said to be sporadic, in which there is no way to establish a single determining factor. Among the scope of possible causes are somatic mutations, accumulated in the breast tissue throughout life. The identification of these mutations allows a better understanding of carcinogenesis and enables the creation of increasingly personalized treatments. The PIK3CA gene, for example, is already determined as a driver (responsible for the selective advantage of a particular clone) for breast cancer. The pathogenic mutations that occur in this gene lead to the activation of Akt / mTOR pathway, among others, which keeps the cell cycle active. One gene that has recently been studied is PRKD1, whose functions seem to be linked to the maintenance of the epithelial phenotype of the mammary tissue cells. Thus, the objective of this work was to identify germline mutations in BRCA1 and BRCA2 genes, also analyzing the family history for breast / ovarian / prostate cancer, and somatic mutations in the PRKD1 gene in postmenopausal patients. Forty-nine patients diagnosed with ipsilateral ductal carcinomas over the age of 54 years who completed NCCN (National Comprehensive Cancer Network) criteria for Breast Cancer and / or Hereditary Ovarian Syndrome and had a tumor paraffin embedded in paraffin collected in the absence of neo adjuvant treatment available. DNA extraction was performed from the peripheral blood for sequencing of BRCA1 and BRCA2, performed through the Ion Torrent (TM) platform or by the Sanger method. The results obtained by Ion Torrent (TM) were first analyzed through the online tool Ion Reporter and those by Sanger through the program Mutation Surveyor v.3.20. The BIC, LOVD, LOVD-IARC, UMD and ClinVar databases were used in addition to the in silico predictors of amino acid conservation among Polyphen-2, SIF, Provean and AlignGVGD species and the effect predictor in the HSF splicing and allelic frequency databases ExAC, 1000 genomes and the NHLBI GO Exome Sequencing Project, following the criteria of the American College of Medical Genetics and Genomics in conjunction with the Association for Molecular Pathology. In order to characterize the somatic mutation of the PRKD1 gene, we determined two regions of greater importance to be sequenced: Ser738 / Ser742 and Ser910 that phosphorylate the protein kinase domain, activating it. Twenty-three tumor samples had DNA extracted. An analysis of PRKD1 information from the COSMIC (Catalog of Somatic Mutations in Cancer) database and the construction of survival curves (Kaplan-Meier) for PRKD1 expression using the online KM Plotter tool was also performed. The median age of the patients was 62 years at diagnosis and 64 years at the time of inclusion in the study. Most of them had tumors of histological grade II (63.27%), clinical stage II (20%) and molecular subtype luminal B (53.06%). Thirty-two reported first-degree relatives affected with breast / ovarian / prostate cancer. Thirty-eight patients had BRCA1 and BRCA2 complete sequencing by Ion Torrent (TM) and eleven had BRCA1 and BRCA2 partial sequencing by Sanger. Pathogenic variants were found in four patients (BRCA1 = 2 / BRCA2 = 2). For PRKD1 sequencing, fifteen patients tumors were sequenced for Ser910 and in eight samples it was possible to analyze the result. No pathogenic variant was found. The data obtained on PRKD1 in COSMIC were: from 2773 samples, in only 15 (0.54%) mutations were identified in PRKD1, 46% (7/15) came from women aged over 55 years and had tumor molecular subtype Luminal. PRKD1 shows higher mutation frequency in cancer of the large intestine (4.22%) and skin (4.02%). The survival curves constructed in KM Plotter demonstrate the high expression of the gene seems to have a positive impact on the patients survival . Despite the low frequency of mutations in PRKD1 gene, other data demonstrate that it appears to play a role of tumor suppressor gene in breast cancer, which must be inhibited by other mechanisms such as DNA methylation