Cancer is a process where the accumulation of several genetic alterations leads to a malignant transformation. Genetic alterations occur randomly at any location in the genome and will most often damage parts that are not of significant importance for the propagation of the cell.
This thesis is comprised of two parts. In the first part we study the influence of four frequently disputed genes on the susceptibility for developing prostate cancer, and in the second part we attempt to establish a basic understanding of the molecular genetic events in penile cancer. In a prostate cancer cohort we have investigated the relation of prostate cancer risk and single nucleotide polymorphisms (SNPs) in four different genes coding for the androgen receptor (AR), the vitamin D receptor (VDR), insulin (INS) and insulin receptor substrate 1 (IRS1)….
Contents
INTRODUCTION
The process of cancer
Prostate cancer, the most common cancer in men
Penile cancer, a rare but psychologically devastating tumour form
GENES OF INTEREST FOR THIS THESIS
Androgen receptor gene
Vitamin D receptor gene
Insulin gene
Two central signalling pathways relaying growth signals
PI3K/AKT pathway
RAS/MAPK pathway
IRS1 gene
PIK3CA gene
PTEN gene
RAS genes
RAF genes
AIMS
STUDY POPULATIONS
Prostate cancer patients (I, II)
Penile cancer patients (III, IV)
Normal control subjects (I, II)
METHODS
DNA isolation (I, II, III, IV)
Whole genome amplification (III)
Single nucleotide polymorphism (I, II)
Single stranded conformation analysis (III)
Sanger chain termination DNA sequencing (III)
Analysis of AR CAG microsatellite (I)
Microarray (IV)
Statistics (I, II)
RESULTS AND DISCUSSION
Short CAG repeat length in the AR gene increases risk of prostate cancer
The TaqI polymorphism in the VDR gene does not modify risk of prostate cancer
The +1127 PstI polymorphism in the insulin gene does not modify risk of prostate
cancer
The G972R polymorphism in the IRS1 gene increases risk of prostate cancer
Mutational status of the PIK3CA gene in prostate cancer
The PIK3CA gene is frequently mutated in penile cancer
RAS mutations in penile cancer
Frequent copy number changes in penile cancer
Candidate genes for penile cancer
Relation of mutations in the PIK3CA and RAS genes and amplification of the
PIK3CA gene
CONCLUSIONS
ACKNOWLEDGEMENTS
REFERENCES
Author: Andersson, Patiyan
Source: Linköping University
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