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KRAS Gene Mutation Analysis, IVD

KRAS Mutation Analysis (RGQ PCR) in Colorectal Cancer (CRC)
KRAS Gene Mutation Analysis, IVD
CPT: 81275; 88381

81275

81275; 88381

Updated on 06/15/2021

Synonyms

KRAS gene sequencing; KRAS exons 2-4 (includes G12C mutation)

KRAS gene sequencing; KRAS exons 2-4 (includes G12C mutation)


Special Instructions

Please provide a copy of the pathology report.


Specimen Requirements


Specimen

Formalin-fixed, paraffin-embedded (FFPE) tissue block or slides from colorectal cancer or NSCLC

Formalin-fixed, paraffin-embedded (FFPE) tissue block with Corresponding H&E slide (preferred ) or unstained slides

Formalin-fixed, paraffin-embedded (FFPE) tissue block or slides from colorectal cancer or NSCLC


Volume

Four unstained slides and one matching H&E-stained slide at 5 µM or formalin-fixed, paraffin-embedded tissue block


Minimum Volume

Two unstained slides and one matching H&E-stained slide at 5 μM. Samples with >4 mm² and ≥20% tumor content are preferred.


Storage Instructions

Store specimen at room temperature. Use cold pack for transport. Be sure cold pack is not in direct contact with specimen during transport.


Causes for Rejection

Tumor block containing no tumor tissue; tumor fixed in a heavy metal fixative; broken or stained slides

Tumor block containing no tumor tissue; tumor fixed in a heavy metal fixative; broken or stained slides


Test Details


Use

The therascreen KRAS RGQ PCR Kit is a real-time qualitative PCR assay used on the Rotor-Gene Q MDx (US) instrument for the detection of 7 somatic mutations in the human KRAS oncogene using DNA extracted from formalin fixed paraffin embedded (FFPE) colorectal cancer (CRC) tissue and non-small cell lung cancer (NSCLC) tissue. The therascreen KRAS RGQ PCR Kit is intended to aid in the identification of CRC patients for treatment with Erbitux® (cetuximab) or with Vectibix® (panitumumab) based on a KRAS No Mutation Detected test result. The therascreen KRAS RGQ PCR Kit is also intended to aid in the identification of NSCLC patients for treatment with LUMAKRAS™ (sotorasib) based on a KRAS G12C Mutation Detected result.

Mutations in the KRAS gene, a known downstream signaling molecule in the EGFR signaling pathway, have been described in approximately 30-50% of colorectal carcinomas.The presence of these mutations correlates with a lack of response for certain EGFR inhibitor cancer therapies in patients with metastatic colorectal cancer: cetuximab (Erbitux®) or panitumimab (Vectibix). Mutations in the KRAS gene are also associated with poor prognosis. As a result, determining the KRAS mutational status of a tumor may guide therapeutic decision making for patients with CRC.

The therascreen KRAS RGQ PCR Kit is a real-time qualitative PCR assay used on the Rotor-Gene Q MDx (US) instrument for the detection of 7 somatic mutations in the human KRAS oncogene using DNA extracted from formalin fixed paraffin embedded (FFPE) colorectal cancer (CRC) tissue and non-small cell lung cancer (NSCLC) tissue. The therascreen KRAS RGQ PCR Kit is intended to aid in the identification of CRC patients for treatment with Erbitux® (cetuximab) or with Vectibix® (panitumumab) based on a KRAS No Mutation Detected test result. The therascreen KRAS RGQ PCR Kit is also intended to aid in the identification of NSCLC patients for treatment with LUMAKRAS™ (sotorasib) based on a KRAS G12C Mutation Detected result.


Limitations

Based on data in the COSMIC database (2012 v59), the seven mutations detected by the KRAS Kit account for >97% of all reported KRAS mutations in CRC patients. The KRAS G12C mutation is estimated to be present in around 13% of NSCLC cases.

Samples with results reported as "no mutation detected" may harbor KRAS mutations that are not detected by the assay.

Detection of mutation is dependent on sample integrity and the amount of amplifiable DNA present in the specimen. The methods used in this assay are highly selective and, depending on the total amount of DNA present, can detect approximately 1% to 5% of mutant DNA in a background of wild-type genomic DNA.

The test is designed to detect 7 mutations in codons 12 and13 of the K-ras gene. These mutations account for >97% of all reported K-ras mutations in CRC patients. Samples with results reported as "no mutation detected" may harbor K-ras mutations that are not detected by the assay.

Based on data in the COSMIC database (2012 v59), the seven mutations detected by the KRAS Kit account for >97% of all reported KRAS mutations in CRC patients. The KRAS G12C mutation is estimated to be present in around 13% of NSCLC cases.

Samples with results reported as "no mutation detected" may harbor KRAS mutations that are not detected by the assay.

Detection of mutation is dependent on sample integrity and the amount of amplifiable DNA present in the specimen. The methods used in this assay are highly selective and, depending on the total amount of DNA present, can detect approximately 1% to 5% of mutant DNA in a background of wild-type genomic DNA.


Methodology

Amplification refractory mutation system (ARMS) and real-time polymerase chain reaction (PCR) using Scorpions™ technology

RotorGene PCR

Amplification refractory mutation system (ARMS) and real-time polymerase chain reaction (PCR) using Scorpions™ technology


References

Arbour KC, Jordan E, Kim HR et al. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2018 Jan 15;24(2):334-340. PubMed 29089357

Bokemeyer C, Van Cutsem E, Rougier P, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomized clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-1475. PubMed 22446022

Catalogue of Somatic Mutations in Cancer (COSMIC). COSMIC web site: www.sanger.ac.uk/genetics/CGP/cosmic. Updated May 28, 2021. Accessed June 2021.

Di Fiore F, Blanchard F, Charbonnier F, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer. 2007 Apr 23;96(8):1166-1169. PubMed 17375050

Qiagen Therascreen KRAS RGQ PCR Kit Instructions for Use (Handbook), June 2021.

Schuch G, Kobold S, Bokemeyer C. Evolving role of cetuximab in the treatment of colorectal cancer. Cancer Manag Res. 2009 Jul 23;1:79-88 PubMed 21188126

Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C, Van Cutsem E. Association of KRAS G13D tumor mutations with outcome in patients with a metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol. 2012 Oct 10;30(29):3570-3577. PubMed 22734028

Arbour KC, Jordan E, Kim HR et al. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2018 Jan 15;24(2):334-340. PubMed 29089357

Bokemeyer C, Van Cutsem E, Rougier P, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomized clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-1475. PubMed 22446022

Catalogue of Somatic Mutations in Cancer (COSMIC). COSMIC web site: www.sanger.ac.uk/genetics/CGP/cosmic. Updated May 28, 2021. Accessed June 2021.

Di Fiore F, Blanchard F, Charbonnier F, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer. 2007 Apr 23;96(8):1166-1169. PubMed 17375050

Qiagen Therascreen KRAS RGQ PCR Kit Instructions for Use (Handbook), June 2021.

Schuch G, Kobold S, Bokemeyer C. Evolving role of cetuximab in the treatment of colorectal cancer. Cancer Manag Res. 2009 Jul 23;1:79-88 PubMed 21188126

Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C, Van Cutsem E. Association of KRAS G13D tumor mutations with outcome in patients with a metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol. 2012 Oct 10;30(29):3570-3577. PubMed 22734028