Development of Molecular Methodologies for the Enhanced Detection of Tumour Biomarkers. Michelle Wood , Hood Mugalassi, Justyna Tull, Linda Meredith, Rachel Butler Institute of Medical Genetics, University Hospital Wales, Cardiff. Lung cancer is the leading cause of cancer deaths.
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
Michelle Wood, Hood Mugalassi, Justyna Tull, Linda Meredith, Rachel Butler
Institute of Medical Genetics, University Hospital Wales, Cardiff
Lung cancer is the leading cause of cancer deaths. Detection of Tumour Biomarkers
NSCLC major subtype.
>70% diagnosed with advanced disease.
5 year survival <15%.
EGFR tyrosine kinase inhibitors (i.e.Gefitinib) used to treat patients refractory to first line chemotherapy.
Response in 10% unselected patients.
Patients with metastic colorectal cancer – 5 yr survival <10%.
Monoclonal antibody therapy targeted to EGF receptor approved for irinotecan resistant mCRC (i.e. Cetuximab).
Response in 10-20% unselected patients.Non Small Cell Lung Cancer and metastatic Colorectal cancer
Mutations in tyrosine kinase domain of EGFR– predict those patients likely to respond to TKI therapy.
90% patients with mutation -15bp deletion in exon 19 or single point mutation in exon 21.
Select patients that will benefit from TKI therapy.EGFR and KRAS mutations
EGFR and KRAS mutations patients likely to respond to TKI therapy.
Nomoto et al. 2006 Am J Clin Pathol126:608-615
Exon 19 Normal
Exon 20 insertions Normal
Comparison of technologies patients likely to respond to TKI therapy.
Li et al. 2008, Nature Medicine 14: 579-584
KRAS mutation patients likely to respond to TKI therapy.
Problems with quality of DNA due to fixation
Mixture of normal and tumour DNA
Long time to process by histopathologists.
Macrodissected to enrich tumour content
Some patients have no tumour sample available
Cell free DNA shed directly from tumour
Extracted from the plasma component of whole blood
Large fragment sizes of tumour DNA possible
Small quantities extracted ~ 100ng/ ml plasmaCell free DNA
Whole blood resections
PlasmaDNA integrity in whole blood and plasma
All Wales medical genetics service resections
Llandoch and Velindra Hospitals, Cardiff
Dr Jason Lester
Dr Mick Button
University Hospital Birmingham
Institute of Molecular Medicine, St James Hospital, Ireland