What Is a KRAS Mutation? KRAS Positivity in Colon and Other Cancers

The KRAS protein is one of the important molecules involved in normal cell growth. Produced under the direction of the KRAS gene, this protein helps transmit signals from outside the cell to its nucleus. When mutated, it drives aggressive cell growth. Mutated KRAS continually sends a “multiply” command even when the cell receives no external signal. KRAS is also responsible for drug resistance that develops against targeted drugs.

In colorectal (colon and rectal) cancer, KRAS mutations are detected in 30-40% of cases; in non-small cell lung cancer, in 10-30%; and in pancreatic cancer, in 90%. These are mutations of the KRAS gene. In addition, 3-4% of people with colon cancer have mutations of the NRAS gene. A mutation in KRAS or NRAS indicates that the patient is unlikely to respond well to anti-EGFR treatments such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs); in other words, it is a biomarkerfor cancer. Therefore, KRAS and NRAS mutation analysis plays a decisive role in treating various cancers, particularly colon and rectal cancer.

KRAS mutations are frequently located in exon 1, at codons 12 (80%) and 13 (15%), and in exon 2, at codon 61. The most frequently observed mutations are Gly12AIa, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val, and Gly13Asp. NRAS mutations are most often observed around codon 61.

When a mutation is present in KRAS or NRAS, it is called mutation-positive; when no mutation is present, it is called wild type .