Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.484917
Title: Molecular cytogenetic studies in the Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma
Author: Chui, Daniel
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2004
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Abstract:
To determine whether recurrent genomic imbalances are a feature of HL, CD30-positive HRS cells were laser microdissected from 20 cHL cases and 4 HL-derived cell lines and subjected to analyses by CGH. In primary tumours, the most frequently involved chromosomal gains were 17q (70%), 2p (40%), 12q (40%), 17p (40%), 22q (35%), 9p (30%), 14q (30%), 16p (30%), with minimal overlapping regions at 17q21, 2p23-13, 12q24, 17p13, 22q13, 9p24-33, 14q32, 16p13.3 and 16p11.2. The most frequent losses involved 13q (35%), 6q (30%), 11q (25%) and 4q (25%), with corresponding minimal overlapping regions at 13q21, 6q22, 11q22 and 4q32. Statistical analysis revealed significantly more gains of 2p and 14q in the older adult cases; loss of 13q was associated with a poor outcome. The results suggest that there is a set of recurrent chromosomal abnormalities associated with cHL and provide further evidence that cHL is genetically distinct from nodular lymphocyte predominance Hodgkin lymphoma (NLPHL). Combined immunophenotype and interphase cytogenetic (FICTION) studies were used as techniques for follow-up studies. High expression of both STAT3 and STAT5a has been described in cHL and their genes are located in 17q21.2. Constitutive activation of NF-?B has been found to be a feature of the HRS cells in cHL and has been shown to facilitate escape from apoptosis. The c-rel gene encodes for a subunit of NF-?B and is located on chromosome 2p16. REL amplification has been shown in some cHL cases. Non-functional inhibitor proteins of NF-?B, such as I?Ba, have been described as an alternative mechanism for the aberrant activation of NF-?B. As part of the follow-up studies, IKBa gene mutation status and loss of heterozygosity (LOH) in the HRS cells were determined by sequence analysis and SNP assays. FICTION confirmed that gains of 2p involved the REL gene but gains on 17q were not due to amplification of STAT3/5a. Frequent IKBa mutations were detected but many are not considered to be of functional importance. REL gain, EBV status, IKBa mutation or LOH were not mutually exclusive mechanisms in the pathogenesis of cHL.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.484917  DOI: Not available
Keywords: QR355 Virology ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)
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