The Leeds Teaching Hospitals NHS Trust

Colorectal Cancer

Metastatic Colorectal Cancer

One of the major advances in the treatment of CRC has been the development of targeted therapies including monoclonal antibodies in metastatic CRC which target the EGFR protein.

Data derived from multiple phase III trials have indicated that KRAS mutations can be considered a highly specific negative biomarker of benefit to anti-EGFR monoclonal antibodies.

ea841a9a0b

Marc Ladanyi, MD

We can offer targetted testing of KRAS, NRAS and BRAF by Next Generation Sequencing which screens for specific reported mutations within codons 12, 13, 59, 61, 117 and 146 of the KRAS gene, codons 12, 13, 59 and 61 of the NRAS gene and codon 600 of the BRAF gene.  Together these account for >95% of all KRAS, NRAS and BRAF mutations in colorectal cancer (Catalogue of Somatic Mutations In Cancer: cancer.sanger.ac.uk/cancergenome/projects/cosmic/).

Recent evidence has suggested that testing one tissue block from colorectal cancers may miss a significant number of RAS and BRAF mutations due to intratumoural heterogeneity (Anal Cell Pathol (Amst) 2011; 34: 61-6). Although the optimum number of tumour blocks to test is not clear, we recommend testing a minimum of two blocks and up to a maximum of five blocks where they are available. RAS and BRAF mutations are believed to be early events and there is no good evidence that testing the diagnostic biopsy, surgical resection or metastatic disease will give differential results. For this reason, we recommend testing multiple blocks from the primary resected tumour to ensure that the tumour is sufficiently sampled, although testing the biopsy and metastatic disease is acceptable if this is the only tumour available.

For the laboratory address and contact details, see the laboratory contacts page.

The standard turnaround time (TAT) from receipt into the genetics lab is generally 7-10 days.