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An investigation into the genetic pathways of colorectal cancer. / Susannah Ruth Fradley
Swansea University Author: Susannah Ruth Fradley
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Abstract
The mortality associated with colorectal cancer is extremely high, however if the disease IS caught at the earliest stage then there is a 95% 5 year survival. An improved screening technique which is less invasive than current methods may increase uptake by the public. Also, an increase in knowledge...
Published: |
2006
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Institution: | Swansea University |
Degree level: | Doctoral |
Degree name: | Ph.D |
URI: | https://cronfa.swan.ac.uk/Record/cronfa42566 |
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2018-08-02T16:24:29.6809968 v2 42566 2018-08-02 An investigation into the genetic pathways of colorectal cancer. 87d2015455021f3f126564dea558d28d NULL Susannah Ruth Fradley Susannah Ruth Fradley true true 2018-08-02 The mortality associated with colorectal cancer is extremely high, however if the disease IS caught at the earliest stage then there is a 95% 5 year survival. An improved screening technique which is less invasive than current methods may increase uptake by the public. Also, an increase in knowledge of the different genetic pathways of colorectal carcinogenesis may help to tailor treatments to individual patients. The experiments in this thesis address these aims by searching for possible biomarkers which may be detectable in stool samples and by looking for early genetic alterations at the molecular, gene expression and chromosomal levels. This thesis also explored various different techniques such as single stranded conformation polymorphism, fragment analysis, sequencing, cDNA arrays and fluorescent in situ hybridisation (FISH). The findings of these experiments include mitochondrial DNA mutations occurring frequently in late stage colorectal carcinogenesis. These mutations predominantly occurred in microsatellites within the mitochondrial genome. Nuclear microsatellite instability (MSI) levels within the South Wales population studied are within the levels found in the rest of the Western world. There was no correlation found between mitochondrial and nuclear MSI suggesting the presence of separate mismatch repair systems. Various genes were found down-regulated in the early stages of colorectal cancer, including PTEN, TGF-BRII and p21. These genes may be key to the early stage development of a significant proportion of colorectal cancers. I developed a FISH probe for p21 which was simple to make and apply, as well as being cost effective. Chromosome 6 aberrations were detected in an increasing frequency in samples with increasingly developed tumours. A large variation was found in chromosome 6 copy number within different regions of an individual tumour. This variation shows how essential it is that research and diagnostic tests are based on either large portions of a tumour or from multiple smaller biopsies. E-Thesis Genetics.;Oncology. 31 12 2006 2006-12-31 COLLEGE NANME Biosciences COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-02T16:24:29.6809968 2018-08-02T16:24:29.6809968 Faculty of Science and Engineering School of Biosciences, Geography and Physics - Biosciences Susannah Ruth Fradley NULL 1 0042566-02082018162504.pdf 10805315.pdf 2018-08-02T16:25:04.5800000 Output 20964181 application/pdf E-Thesis true 2018-08-02T16:25:04.5800000 false |
title |
An investigation into the genetic pathways of colorectal cancer. |
spellingShingle |
An investigation into the genetic pathways of colorectal cancer. Susannah Ruth Fradley |
title_short |
An investigation into the genetic pathways of colorectal cancer. |
title_full |
An investigation into the genetic pathways of colorectal cancer. |
title_fullStr |
An investigation into the genetic pathways of colorectal cancer. |
title_full_unstemmed |
An investigation into the genetic pathways of colorectal cancer. |
title_sort |
An investigation into the genetic pathways of colorectal cancer. |
author_id_str_mv |
87d2015455021f3f126564dea558d28d |
author_id_fullname_str_mv |
87d2015455021f3f126564dea558d28d_***_Susannah Ruth Fradley |
author |
Susannah Ruth Fradley |
author2 |
Susannah Ruth Fradley |
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E-Thesis |
publishDate |
2006 |
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Swansea University |
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Faculty of Science and Engineering |
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facultyofscienceandengineering |
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Faculty of Science and Engineering |
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facultyofscienceandengineering |
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Faculty of Science and Engineering |
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School of Biosciences, Geography and Physics - Biosciences{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Biosciences, Geography and Physics - Biosciences |
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description |
The mortality associated with colorectal cancer is extremely high, however if the disease IS caught at the earliest stage then there is a 95% 5 year survival. An improved screening technique which is less invasive than current methods may increase uptake by the public. Also, an increase in knowledge of the different genetic pathways of colorectal carcinogenesis may help to tailor treatments to individual patients. The experiments in this thesis address these aims by searching for possible biomarkers which may be detectable in stool samples and by looking for early genetic alterations at the molecular, gene expression and chromosomal levels. This thesis also explored various different techniques such as single stranded conformation polymorphism, fragment analysis, sequencing, cDNA arrays and fluorescent in situ hybridisation (FISH). The findings of these experiments include mitochondrial DNA mutations occurring frequently in late stage colorectal carcinogenesis. These mutations predominantly occurred in microsatellites within the mitochondrial genome. Nuclear microsatellite instability (MSI) levels within the South Wales population studied are within the levels found in the rest of the Western world. There was no correlation found between mitochondrial and nuclear MSI suggesting the presence of separate mismatch repair systems. Various genes were found down-regulated in the early stages of colorectal cancer, including PTEN, TGF-BRII and p21. These genes may be key to the early stage development of a significant proportion of colorectal cancers. I developed a FISH probe for p21 which was simple to make and apply, as well as being cost effective. Chromosome 6 aberrations were detected in an increasing frequency in samples with increasingly developed tumours. A large variation was found in chromosome 6 copy number within different regions of an individual tumour. This variation shows how essential it is that research and diagnostic tests are based on either large portions of a tumour or from multiple smaller biopsies. |
published_date |
2006-12-31T03:53:13Z |
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1763752640011829248 |
score |
11.021648 |