The KRAS (KRAS proto-oncogene, GTPase) gene located on chromosome 12p12.1 is a member of the RAS gene family comprising HRAS, KRAS, and NRAS, all of which encode a 21 kDa protein. The wildtype proteins play a pivotal role in cell proliferation, differentiation, and senescence.

Mutations of KRAS are frequently found in epithelial malignancies and lead to activation of the downstream mitogen-activated protein kinase (MAPK) resulting in unchecked cellular proliferation and tumor progression.

Amplifications of KRAS and the impli-cations in tumorigenesis are not as well characterized as KRAS mutations.

However, recent studies using different methods found amplification of KRAS or copy number gain of the 12p12.1 region including KRAS in various primary tumors, as e.g. in lung, colorectal, pancreatic, and gastric cancers.

For non-small cell lung cancer (NSCLC) patients KRAS amplification as assessed by Fluorescence in situ Hybridization (FISH) was detected in about 15% of the tumors. Amplification of KRAS was found to be correlated with poor prognosis and may act synergistically with KRAS mutations to promote tumor progression.