Studying the molecular pathology of cytological samples from pancreatic and biliary ducts

Despite general development in cancer diagnostics pancreatic cancer remains one of the cancers with the poorest prognosis. The diagnosis is usually done in a late stage as reliable screening methods are not available. Resection increases the five year survival rate from 5% to 20% but only one in fiv...

Full description

Bibliographic Details
Main Author: Mäkinen, Erna
Other Authors: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Format: Master's thesis
Language:eng
Published: 2018
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/60908
_version_ 1826225769924263936
author Mäkinen, Erna
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Mäkinen, Erna Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Mäkinen, Erna Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Mäkinen, Erna
datasource_str_mv jyx
description Despite general development in cancer diagnostics pancreatic cancer remains one of the cancers with the poorest prognosis. The diagnosis is usually done in a late stage as reliable screening methods are not available. Resection increases the five year survival rate from 5% to 20% but only one in five pancreatic cancers is detected when the surgical resection is still possible. KRAS mutation is present in almost all cases and TP53, CDKN2A and SMAD4 mutations are common (40-60% of cases). A cytological brush sample can be obtained from pancreatic and biliary ducts. The sample is usually low in cellularity and microscopic diagnosis alone may be inconclusive. The inclusion of molecular pathology methods could clarify the diagnosis. The aim of this Master's Thesis was to study if pancreatic cancer associated mutations were detectable from the cytological samples and to evaluate the value and sensitivity of the molecular diagnostic methods used. 30 cytological samples from pancreatic and biliary ducts of pancreatic cancer patients were studied with droplet digital PCR (ddPCR) and next generation sequencing (NGS). KRAS mutation was detected in 63,3% with ddPCR and 57% with NGS. With NGS a mutation in TP53, CDKN2A and SMAD4 was found in 60%, 40% and 30% of the cases, respectively. In conclusion, the sensitivity of ddPCR was higher than NGS but neither were highly sensitive when studying KRAS mutation from samples with low tumor DNA yield. KRAS mutation was found to be unspecific for malignancy as it was found from 33% of 24 benign control samples studied with ddPCR. TP53, CDKN2A, and SMAD4 were detected with similar frequency than in literature when using NGS. Cytological samples hold potential for diagnostic use when suitable biomarkers and sensitive methods are used.
first_indexed 2019-09-20T09:14:55Z
format Pro gradu
free_online_boolean 1
fullrecord [{"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": "M\u00e4kinen, Erna", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2019-01-04T10:32:39Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2019-01-04T10:32:39Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2018", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/60908", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Despite general development in cancer diagnostics pancreatic cancer remains one of the cancers with the poorest prognosis. The diagnosis is usually done in a late\nstage as reliable screening methods are not available. Resection increases the five year survival rate from 5% to 20% but only one in five pancreatic cancers is detected when the surgical resection is still possible. KRAS mutation is present in almost all cases and TP53, CDKN2A and SMAD4 mutations are common (40-60% of cases). A cytological brush sample can be obtained from pancreatic and biliary ducts. The sample is usually low in cellularity and microscopic diagnosis alone may be inconclusive. The inclusion of molecular pathology methods could clarify the diagnosis. The aim of this Master's Thesis was to study if pancreatic cancer associated mutations were detectable from the cytological samples and to evaluate the value and sensitivity of the molecular diagnostic methods used. 30 cytological samples from pancreatic and biliary ducts of pancreatic cancer patients were studied with droplet digital PCR (ddPCR) and next generation sequencing (NGS). KRAS mutation was detected in 63,3% with ddPCR and 57% with NGS. With NGS a mutation in TP53, CDKN2A and SMAD4 was found in 60%, 40% and 30% of the cases, respectively. In conclusion, the sensitivity of ddPCR was higher than NGS but neither were highly sensitive when studying KRAS mutation from samples\nwith low tumor DNA yield. KRAS mutation was found to be unspecific for malignancy as it was found from 33% of 24 benign control samples studied with ddPCR. TP53, CDKN2A, and SMAD4 were detected with similar frequency than in literature when using NGS. Cytological samples hold potential for diagnostic use when suitable biomarkers and sensitive methods are used.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Miia Hakanen (mihakane@jyu.fi) on 2019-01-04T10:32:39Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2019-01-04T10:32:39Z (GMT). No. of bitstreams: 0\n Previous issue date: 2018", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "42", "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": "ERCP", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "TP53", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "SMAD4", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "CDKN2A", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "KRAS", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "droplet digital PCR", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "next generation sequencing", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Studying the molecular pathology of cytological samples from pancreatic and biliary ducts", "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-201901041074", "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.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "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": "openAccess", "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": "haimasy\u00f6p\u00e4", "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": "geenit", "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": "molekyylibiologia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "haima", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "pancreatic cancer", "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": "genes", "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": "molecular biology", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "pancreas", "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.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
id jyx.123456789_60908
language eng
last_indexed 2025-02-18T10:56:05Z
main_date 2018-01-01T00:00:00Z
main_date_str 2018
online_boolean 1
online_urls_str_mv {"url":"https:\/\/jyx.jyu.fi\/bitstreams\/afd31915-c41e-41cb-a8b9-e1830c4f42fd\/download","text":"URN:NBN:fi:jyu-201901041074.pdf","source":"jyx","mediaType":"application\/pdf"}
publishDate 2018
record_format qdc
source_str_mv jyx
spellingShingle Mäkinen, Erna Studying the molecular pathology of cytological samples from pancreatic and biliary ducts ERCP TP53 SMAD4 CDKN2A KRAS droplet digital PCR next generation sequencing Solu- ja molekyylibiologia Cell and molecular biology 4013 haimasyöpä mutaatiot geenit DNA molekyylibiologia haima pancreatic cancer mutations genes molecular biology pancreas
title Studying the molecular pathology of cytological samples from pancreatic and biliary ducts
title_full Studying the molecular pathology of cytological samples from pancreatic and biliary ducts
title_fullStr Studying the molecular pathology of cytological samples from pancreatic and biliary ducts Studying the molecular pathology of cytological samples from pancreatic and biliary ducts
title_full_unstemmed Studying the molecular pathology of cytological samples from pancreatic and biliary ducts Studying the molecular pathology of cytological samples from pancreatic and biliary ducts
title_short Studying the molecular pathology of cytological samples from pancreatic and biliary ducts
title_sort studying the molecular pathology of cytological samples from pancreatic and biliary ducts
title_txtP Studying the molecular pathology of cytological samples from pancreatic and biliary ducts
topic ERCP TP53 SMAD4 CDKN2A KRAS droplet digital PCR next generation sequencing Solu- ja molekyylibiologia Cell and molecular biology 4013 haimasyöpä mutaatiot geenit DNA molekyylibiologia haima pancreatic cancer mutations genes molecular biology pancreas
topic_facet 4013 CDKN2A Cell and molecular biology DNA ERCP KRAS SMAD4 Solu- ja molekyylibiologia TP53 droplet digital PCR geenit genes haima haimasyöpä molecular biology molekyylibiologia mutaatiot mutations next generation sequencing pancreas pancreatic cancer
url https://jyx.jyu.fi/handle/123456789/60908 http://www.urn.fi/URN:NBN:fi:jyu-201901041074
work_keys_str_mv AT mäkinenerna studyingthemolecularpathologyofcytologicalsamplesfrompancreaticandbiliaryducts