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Title: Molecular profiling of primary head and neck squamous cell carcinoma and lymph node metastases
Author: Sethi, Neeraj
ISNI:       0000 0004 5918 1504
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2015
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INTRODUCTION: The presence of lymph node metastases and/or extracapsular spread (ECS) has a significant impact on patient survival in Head and neck squamous cell carcinoma (HNSCC). Little is known about the molecular mechanisms associated with metastasis. A marker that could predict metastasis from primary tumour sampling could be of great clinical benefit for patients. Similarly in oropharyngeal squamous cell carcinoma (OPSCC), the molecular changes associated with human papilloma virus are incompletely understood. The impact of viral load has not been well explored and could help identify molecular markers associated with Human papillomavirus (HPV)-driven OPSCC. METHODS: Tissue samples were identified from Leeds Pathology Archive and nucleic acid extracted from these. This was processed into sequencing libraries and analysed for copy number alteration (CNA) and microRNA (miRNA) profiles in clinicopathologic groups relating to metastasis and HPV viral load. RESULTS: A panel of 14 CNAs was identified as associated with nodal metastasis and loss of 18q21.1-q21.32 was associated with ECS. The fraction of genome altered (FGA) was also increased in metastatic primary tumours. A panel of 19 CNAs was identified as associated with no detectable viral load and the FGA was found to be increased in this group of OPSCC. Twelve miRNAs were identified as associated with nodal metastasis. DISCUSSION: The CNA and miRNA profile of primary tumours was found to be largely similar, though not identical, highlighting the need to use metastatic tissue to attempt discovery of metastatic molecular markers. Integrating miRNA and CNA data suggested miRNA expression is not governed by CNA. Potentially translational marker for metastasis and OPSCC with no viral load have been identified.
Supervisor: Wood, Henry ; Bishop, Timothy ; Rabbitts, Pamela ; MacLennan, Kenneth Sponsor: Leeds Teaching Hospitals Charitable Foundation ; Mason Medical Research Foundation ; Royal College of Physicians and Surgeons of Glasgow ; University of Leeds
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available