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[{"key": "dc.contributor.advisor", "value": "Kuopio, Teijo", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Lahtinen, Laura", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Mustam\u00e4ki, Taru", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2020-06-29T05:49:12Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2020-06-29T05:49:12Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2020", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/70949", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Primaarinen sklerosoiva kolangiitti, eli PSC on krooninen tulehduksellinen sappiteiden sairaus, joka aiheuttaa sappiteihin arpeutumista ja ahtaumia. PSC potilaista 20 % saa pel\u00e4ttyn\u00e4 huonoennusteisena komplikaationa sappitiesy\u00f6v\u00e4n eli kolangiokarsinooman. Kolangiokarsinooman katsotaan kehittyv\u00e4n kroonisen tulehduksen aiheuttamien sappiteiden muutosten, sek\u00e4 DNA-vaurioiden seuraksena. Taudin kehityskulku on vaiheittainen, jossa sappiteiden epiteelisolujen sy\u00f6v\u00e4n esiasteet, eli dysplasiat edelt\u00e4v\u00e4t sy\u00f6v\u00e4n syntymist\u00e4. Ainoa parantava hoito kolangiokarsinoomaan on maksansiirto, joka tulisi suorittaa oikea-aikaisesti jo ennen sy\u00f6v\u00e4n kehittymist\u00e4. On haastavaa erottaa toisistaan hyv\u00e4nlaatuiset sappiteiden ahtaumat ja sy\u00f6p\u00e4solukko. Edes erilaisia diagnostisia menetelmi\u00e4 yhdist\u00e4m\u00e4ll\u00e4 ei saada kolangiokarsinoomaa havaittua tarpeeksi ajoissa, jotta maksansiirron ajankohta voidaan optimoida. K\u00e4yt\u00f6ss\u00e4 on kuvantamisen menetelmi\u00e4, sytologiaa ja erilaisia biomarkkereita, mutta niidenkin yhdistelmill\u00e4 on haastavaa havaita kolangiokarsinooman kehittyminen varhaisessa vaiheessa. Kolangiokarsinoomassa tyypillisesti esiintyvi\u00e4 geneettisi\u00e4 muutoksia on l\u00f6ydetty useista geeneist\u00e4, kuten KRAS-, TP53-, FBXW7-, CDKN2A- ja SMAD4 -geeneist\u00e4. Nykytekniikoilla, kuten uuden sukupolven sekvensoinnilla (NGS), sek\u00e4 emulsiopohjaisella digitaalisella polymeraasiketjureaktiolla (ddPCR) mutaatioita voidaan tutkia erilaisista n\u00e4ytteist\u00e4. T\u00e4ss\u00e4 ty\u00f6ss\u00e4 tutkimme nelj\u00e4\u00e4n eri kategoriaan (ei dysplasiaa, liev\u00e4 dysplasia, vaikea dysplasia ja kolangiokarsinooma) kuuluvia sy\u00f6v\u00e4ksi edenneit\u00e4 n\u00e4ytteit\u00e4 vuosilta 2007-2018 ja pyrimme l\u00f6yt\u00e4m\u00e4\u00e4n kolangiokarsinooman tunnettuja mutaatioita n\u00e4ist\u00e4 n\u00e4ytteist\u00e4 NGS- ja ddPCR -menetelmill\u00e4. Emme l\u00f6yt\u00e4neet tietty\u00e4 kolangiokarsinooman synty\u00e4 ennustavaa yhteist\u00e4 muutosta n\u00e4ytteist\u00e4, mutta tuloksissa oli monia kiinnostavia mahdollisesti tautia aiheuttavia geenivariantteja. Aiempien tutkimusten perusteella odotimme l\u00f6yt\u00e4v\u00e4mme KRAS-mutaatioita n\u00e4ytteist\u00e4, mutta vain muutama n\u00e4yte oli KRAS-mutaatiopositiivinen NGS-menetelm\u00e4ll\u00e4. N\u00e4ytteiden ik\u00e4, sek\u00e4 pienet DNA saannot n\u00e4ytemateriaalista n\u00e4yttiv\u00e4t vaikuttavan sekvensointituloksiin negatiivisesti. ddPC oli herkempi menetelm\u00e4 ja osoitti KRAS-mutaatioita useista n\u00e4ytteist\u00e4. Kolangiokarsinoomaan johtavien aikaisten muutosten tutkiminen on t\u00e4rke\u00e4\u00e4 ja parempilaatuisesta alkumateriaalista geenimuutosten l\u00f6yt\u00e4minen voi onnistua paremmin.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the liver and it causes fibrosis and strictures in the bile ducts. Cholangiocarcinoma (CCA) is the most significant cause of early death in PSC patients and 20 % of the patients will develop CCA as a complication of PSC. Pathogenesis of PSC associated CCA is believed to be driven by the chronic inflammation of PSC. DNA damages lead to CCA through dysplasia-carcinoma sequence. CCA is a cancer with poor prognosis and only curative treatment is liver transplantation (LT) on early stage. It is challenging to distinguish benign PSC lesions from premalignant or malignant even with various combinations of diagnostic methods such as computed tomography, magnetic imaging, endoscopic retrograde cholangiography, brush cytology, flow cytometry and different biomarkers. Early diagnostic methods for surveillance of malignancy in PSC patients is much needed. Genetic alterations in PSC associated CCA such as KRAS, TP53, FBXW7, CDKN2A and SMAD4 have been found in CCA tumors. Mutations can be studied with sensitive methods like next generation sequencing (NGS) and droplet digital PCR (ddPCR). In this work the aim was to study FFPE brush cytology samples from PSC patients in four categories (no dysplasia, low-grade dysplasia, high-grade dysplasia and CCA) where the end result had been CCA in between years 2007 to 2018. The goal was to study with NGS and ddPCR if CCA linked mutations could be found in dysplasia samples to predict the development of CCA. No clear cancer predictive marker variants were found in the NGS data but multiple pathogenic or possibly pathogenic variants were present. We hypothesized to find KRAS mutations in the samples since they are very frequent in CCA tumours. However due to the low DNA yields and the age of the samples only a few samples tested positive for KRAS. ddPCR had higher sensitivity for detecting KRAS from these scarce samples. More research with better sample quality is needed to study these variants that can be detected already in dysplasia stages.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Miia Hakanen (mihakane@jyu.fi) on 2020-06-29T05:49:12Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2020-06-29T05:49:12Z (GMT). No. of bitstreams: 0\n Previous issue date: 2020", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "43", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "PSC", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "CCA", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "NGS", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "ddPCR", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Primary sclerosing cholangitis dysplasia-carcinoma sequence : possibilities in early stage molecular pathology", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202006295135", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.collaborator", "value": "business", "language": "", "element": "contractresearch", "qualifier": "collaborator", "schema": "yvv"}, {"key": "yvv.contractresearch.collaborator", "value": "public", "language": "", "element": "contractresearch", "qualifier": "collaborator", "schema": "yvv"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "yvv.contractresearch.initiative", "value": "business", "language": "", "element": "contractresearch", "qualifier": "initiative", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "sy\u00f6p\u00e4taudit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "DNA", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "mutaatiot", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "dysplasiat", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "sappitiet", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "diagnostiikka", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "cancerous diseases", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "DNA", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "mutations", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "dysplasia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "bile ducts", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "diagnostics", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "The author has not given permission to make the work publicly available electronically. Therefore the material can be read only at the archival workstation at Jyv\u00e4skyl\u00e4 University Library (https://kirjasto.jyu.fi/en/workspaces/facilities).", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Tekij\u00e4 ei ole antanut lupaa avoimeen julkaisuun, joten aineisto on luettavissa vain Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6semalta. Ks. https://kirjasto.jyu.fi/fi/tyoskentelytilat/laitteet-ja-tilat..", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
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