Molecular Characterization of Circulating Tumor Cells (CTCs) in Patients with Early Prostate Cancer

Postgraduate Thesis uoadl:1319116 299 Read counter

Unit:
Κατεύθυνση Κλινική Χημεία
Library of the School of Science
Deposit date:
2015-10-15
Year:
2015
Author:
Παρασκευόπουλος Παναγιώτης
Supervisors info:
Ε.Λιανίδου, Καθηγήτρια
Original Title:
Μοριακός Χαρακτηρισμός Κυκλοφορούντων Καρκινικών Κυττάρων (CTCs) Ασθενών με Πρώιμο Καρκίνο Προστάτη
Languages:
Greek
Translated title:
Molecular Characterization of Circulating Tumor Cells (CTCs) in Patients with Early Prostate Cancer
Summary:
Prostate cancer is considered to be the second lethal cancer among men while it
is estimated that one out of six men will be newly diagnosed with the disease.
It is widely accepted that the main cause of death among cancer patients is the
metastatic disease. The initiation of minimal residual disease (MRD) and
especially the detection of circulating tumor cells (CTCs) in patients’
peripheral blood represents a negative prognostic parameter for recurrence-free
survival. CTCs could serve as a “liquid biopsy” that provide the opportunity to
noninvasively and repeatedly sample representative tumor cells, providing
information concerning not only tumor burden but also the heterogeneity and the
progression of the tumor. The combination of both genetic and epigenetic
alternations has been correlated with the initiation and the progression of
carcinogenesis. The aim of this diploma thesis was the molecular
characterization of CTCs in early prostate cancer patients. CTCs were isolated
with a novel in vivo device CellCollector TM (Gilupi) from patients with
primary prostate cancer. To be more precise, we sought to assess the expression
of the fusion gene TMPRSS2-ERG (T1/E4) and the methylation status of the GSTP1
gene. For the study of the expression of the TMPRSS2-ERG (T1/E4) fusion gene we
developed, optimized and applied a RT-qPCR methodology. The developed
methodology was analytically optimized, validated and then applied to 24
CTC-samples. None of these samples was found positive for the expression of the
fusion gene TMPRSS2-ERG (T1/E4) (0/24, 0%). The promoter of the GSTP1 gene has
an extended CpG island region which is frequently hypermethylated in prostate
cancer cells leading to its transcriptional silencing. The methylation status
of the GSTP1 promoter was evaluated by a real time MSP methodology which was
optimized regarding its analytical characteristics and applied in 53
CTC-samples. Methylation of GSTP1 promoter was observed in 7 samples (7/53,
13.2%).
Keywords:
CTCs, TMPRSS2-ERG (T1/E4), GSTP1, RT-qPCR, qMSP
Index:
Yes
Number of index pages:
VII-XVIII
Contains images:
Yes
Number of references:
166
Number of pages:
XVIII,136
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