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The pathogenesis of classical Hodgkin lymphoma : investigation of possible viral pathogens and recurrent chromosomal imbalances

Wilson, Katherine Sarah (2008) The pathogenesis of classical Hodgkin lymphoma : investigation of possible viral pathogens and recurrent chromosomal imbalances. PhD thesis, University of Glasgow.

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Abstract

Hodgkin lymphoma (HL) is a malignant lymphoma that is diagnosed mostly in young adults, and is the second most common malignancy to affect this age group. This disease is subdivided into two entities with different aetiologies: classical HL (cHL) (~95% of cases) and nodular lymphocyte-predominant HL. In Europe, ~82% of young adults with cHL are non-Epstein-Barr virus associated and epidemiological studies have suggested that a common infectious agent may play a key role in the aetiology of these cases. The molecular biology of HL is not well understood, primarily due to the low number of Hodgkin and Reed-Sternberg (HRS) cells present within these tumours. However, recently developed techniques for the selection and micromanipulation of single HRS cells from tumours, and the development of molecular cytogenetic techniques (i.e. array-comparative genomic hybridisation (CGH) are overcoming these difficulties. To investigate a potential candidate virus, DNA samples from cHL biopsies were screened for the measles virus (MV) and polyomaviruses (PyV), using immunohistochemistry and highly sensitive PCR assays. Chromosomal imbalances in six well-established cHL-derived cell lines and a cHL case were analysed by array-CGH. To obtain sufficient DNA for array-CGH from the cHL case, single HRS cells were isolated using laser microdissection. DNA was extracted then amplified by degenerate oligonucleotide primer polymerase chain reaction. MV and PyV genomes were not detected within cHL biopsies. Recurrent chromosomal imbalances were confirmed within the cHL-derived cell lines and cHL case, in addition to several novel imbalances. This is the first time that a cHL case has been analysed by array-CGH.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: R Medicine > RB Pathology
Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Supervisor's Name: Jarrett, Professor Ruth
Date of Award: 2008
Depositing User: Mrs Marie Cairney
Unique ID: glathesis:2008-488
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 20 Nov 2008
Last Modified: 10 Dec 2012 13:19
URI: http://theses.gla.ac.uk/id/eprint/488

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