KRAS mutation and EGFR inhibitor response

KRAS

Test Synonym:

K-ras

Associations:

Colorectal cancer

CPT Code:

83891 – DNA isolation
83896 x 8 – Nucleic acid hybridization
83898 x 8 – PCR amplification
838907 – Cell Lysis
838912 – Interpretation and Report

Turnaround Time:

8-10 days

Methodology:

Real-Time PCR based SNP assay platform

Specimen Requirements:

10% neutral buffered formalin fixed paraffin embedded tissue with minimum of 20% tumor involvement.

Causes for Rejection:

Improper specimen labeling; insufficient sample; inadequate fixation and/or processing

Specimen Stability:

Paraffin block stable indefinitely at ambient temperature

Storage and Handling:

Ship ambient. In warm weather ship in a Styrofoam container with an ice pack (do not allow ice pack to directly contact sample)

Reference Range:

The assay detects 7 mutations found in codon 12 and 13 of the K-RAS oncogene

Gly12Asp (GGT>GAT)
Gly12Ala (GGT>GCT)
Gly12Val (GGT>GTT)
Gly12Ser (GGT>AGT)
Gly12Arg (GGT>CGT)
Gly12Cys (GGT>TGT)
Gly12Asp (GGC>GAC)

Indication:

K-RAS mutation testing assists with the identification of colorectal cancer (CRC) patients most likely to show limited clinical response to anti-epidermal growth factor receptor (anti-EGFR) therapies.
Recent studies have demonstrated that the K-RAS gene is mutated in approximately 35 to 45% of colorectal carcinomas and that the determination of K-RAS mutation status in CRC patients can better define those who will benefit from treatment with anti-EGFR monoclonal antibody therapies such as Erbitux® (cetuximab) and Vectibix® (panitumumab). This molecular test detects seven somatic mutations commonly found in the K-RAS oncogene.

References:

Baselga J. et al. 2008. Determinants of RASistance to anti-epidermal growth factor receptor agents. Journal of Clinical Oncology 26(10): 1582-1584
Janmatt ML et al. 2003. Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. Clinical Cancer Research, 9:2316-2326
Khambata-Ford S. et al. 2007. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. Journal of Clinical Oncology 25(22):3230-3237
Lievre A. et al. 2008. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treatment with cetuximab. Journal of Clinical Oncology 26(3):374-379
Massarelli E. et al. 2007. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clinical Cancer Res 13(10):2890-2896