Targeted Oncogene Mutation Detection in Non-small Cell Lung Cancer by Multiplexed Array Mass Spectrometry Genotyping: Results of a Clinical Validation Study
| aut.embargo | No | en_NZ |
| aut.thirdpc.contains | No | en_NZ |
| aut.thirdpc.permission | No | en_NZ |
| aut.thirdpc.removed | No | en_NZ |
| dc.contributor.advisor | McKeage, Mark | |
| dc.contributor.advisor | Li, Yan | |
| dc.contributor.author | Shepherd, Phillip | |
| dc.date.accessioned | 2017-10-29T22:04:35Z | |
| dc.date.available | 2017-10-29T22:04:35Z | |
| dc.date.copyright | 2017 | |
| dc.date.created | 2017 | |
| dc.date.issued | 2017 | |
| dc.date.updated | 2017-10-28T02:40:35Z | |
| dc.description.abstract | Cancer is the second leading cause of death in New Zealand and despite being the fifth most commonly diagnosed cancer, lung cancers are the leading cause of cancer related deaths and one of the major health issues affecting New Zealand (Ministry of Health, 2016). The relatively recent discovery of cancer driver genes and somatic mutations in lung cancer patient sub-groups has seen the emergence of genetic abnormalities being used in the treatment of lung cancer as predictive bio-markers and molecular targets for targeted cancer therapy especially in Non-small Cell Lung Cancer (NSCLC) (Mitsudomi & Yatabe, 2010). There are several different technologies available for the detection of Epidermal Growth Factor Receptor (EGFR) mutations in NSCLC. The Roche Cobas EGFR gene mutation test and Agena Mass Array OncoFocus gene mutation assay are two examples of these technologies. There is very little in the literature in relation to the cross validation of these technologies. The aim of this thesis was to provide this validation data while also ensuring the clinical utility of such testing. The study consisted of 532 patients that were both tested by using the Roche Cobas EGFR gene mutation test and retested using the Agena Mass Array OncoFocus gene mutation assay. To evaluate the diagnostic accuracy of this novel genetic testing strategy, data was analysed by agreement analysis. Overall survival and progression free survival after gefitinib or erlotinib treatment were analysed with the Kaplan–Meier method to assess the time to death or progression. Cox-regression was used for multivariate survival analysis. A log-rank test was employed to compare cumulative survival in different groups. All P-values were two-sided and a P-value <0.05 was considered statistically significant. There was moderately high agreement between the Cobas EGFR Mutation Test and the Agena Mass Array OncoFocus assay for the detection of EGFR mutations in this study. There was a very high level of agreement between the Cobas EGFR Mutation Test and the Agena Mass Array OncoFocus assay for the identification of specific EGFR mutations in patient samples that were mutation-positive in both assays. The clinical validity of the assay was established by demonstrating high levels of overall agreement in the detection of EGFR mutations compared to a reference assay. This study has demonstrated the clinical validity and utility of the Agena Mass Array OncoFocus assay for detecting EGFR mutations in tumour specimens from NSCLC patients. In addition to ERFR mutations the Agena Mass Array OncoFocus assay identified a large number of patient samples with KRAS, NRAS and BRAF mutations that were not tested for by the Cobas EGFR Mutation Test. These mutations were also found by the study to have clinical relevance. In conclusion the validity of the Agena Mass Array OncoFocus assay for detecting not only EGFR but also KRAS, NRAS & BRAF mutations in NSCLC tumour specimens, and the potential clinical usefulness for prediction of prognosis and clinical benefits from EGFR-TKI treatment has been demonstrated. | en_NZ |
| dc.identifier.uri | https://hdl.handle.net/10292/10925 | |
| dc.language.iso | en | en_NZ |
| dc.publisher | Auckland University of Technology | |
| dc.rights.accessrights | OpenAccess | |
| dc.subject | Agena Mass Array | en_NZ |
| dc.subject | NSCLC | en_NZ |
| dc.subject | EGFR | en_NZ |
| dc.subject | FFPE EGFR | en_NZ |
| dc.subject | Sequenom | en_NZ |
| dc.title | Targeted Oncogene Mutation Detection in Non-small Cell Lung Cancer by Multiplexed Array Mass Spectrometry Genotyping: Results of a Clinical Validation Study | en_NZ |
| dc.type | Thesis | |
| thesis.degree.grantor | Auckland University of Technology | |
| thesis.degree.level | Masters Theses | |
| thesis.degree.name | Master of Medical Laboratory Science | en_NZ |