Pyrosequencing-based methods reveal marked inter-individual differences in oncogene mutation burden in human colorectal tumours View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-07

AUTHORS

S Weidlich, K Walsh, D Crowther, M E Burczynski, G Feuerstein, F A Carey, R J C Steele, C R Wolf, G Miele, G Smith

ABSTRACT

BACKGROUND: The epidermal growth factor receptor-targeted monoclonal antibody cetuximab (Erbitux) was recently introduced for the treatment of metastatic colorectal cancer. Treatment response is dependent on Kirsten-Ras (K-Ras) mutation status, in which the majority of patients with tumour-specific K-Ras mutations fail to respond to treatment. Mutations in the oncogenes B-Raf and PIK3CA (phosphoinositide-3-kinase) may also influence cetuximab response, highlighting the need for a sensitive, accurate and quantitative assessment of tumour mutation burden. METHODS: Mutations in K-Ras, B-Raf and PIK3CA were identified by both dideoxy and quantitative pyrosequencing-based methods in a cohort of unselected colorectal tumours (n=102), and pyrosequencing-based mutation calls correlated with various clinico-pathological parameters. RESULTS: The use of quantitative pyrosequencing-based methods allowed us to report a 13.7% increase in mutation burden, and to identify low-frequency (<30% mutation burden) mutations not routinely detected by dideoxy sequencing. K-Ras and B-Raf mutations were mutually exclusive and independently associated with a more advanced tumour phenotype. CONCLUSION: Pyrosequencing-based methods facilitate the identification of low-frequency tumour mutations and allow more accurate assessment of tumour mutation burden. Quantitative assessment of mutation burden may permit a more detailed evaluation of the role of specific tumour mutations in the pathogenesis and progression of colorectal cancer and may improve future patient selection for targeted drug therapies. More... »

PAGES

246

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2011.197

DOI

http://dx.doi.org/10.1038/bjc.2011.197

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000088800

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21712828


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