KRAS Mutations (DNA)

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General Information

Lab Name
KRAS Mutations
Lab Code
KRAS
Epic Ordering
Order using "UW Genetics and Solid Tumor Test Request"

For solid tumors only. Use Heme Single Gene by NGS [HCAPSG] for hematopoietic malignancies.

See tip sheet for more information (internal link).

Description

Please note that KRAS Mutations is intended for solid tumors, for testing related to hematologic malignancies, please order - Heme Single Gene by NGS [HCAPSG]. Consultation with a Director can be requested to determine the appropriate testing. Please contact the laboratory at 206-598-6429 for further questions.

This test detects mutations in exons 2, 3, and 4 of the KRAS gene, which includes codons 12, 13, 59, 61, 117, and 146. Acquired KRAS mutations at these codons are associated with resistance to drugs that target the epidermal growth factor receptor (including cetuximab and panitumumab). KRAS p.G12C mutations in lung canacers have been associated with efficacy of specific inhibitors (e.g. sotorasib). This test can normally detect a heterozygous mutation if it is present in more than about 10% of the cells in the sample.

References
  • Skoulidis F, et al. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 384(25):2371-2381. PMID: 34096690
  • Karapetis CS, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008, 359:1757-65. 18946061
  • Lièvre A, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008, 26:374-9. 18202412
  • Also see correspondence for a good meta-analysis: J Clin Oncol 2008;26:2601-2602.
    Forms & Requisitions

    Genetics Requisition

    Providers with access to the UW implementation of Epic (i.e., FHCC, HMC, SCCA, UWMC, UWNW) may order this test using the order "UW Genetics and Solid Tumor Test Request." See tip sheet for more information (internal link).

    Synonyms
    cetuximab, colorectal cancer, erbitux, extended RAS, G12C, Gynecological Oncology Pathway, GYNPTH, K-RAS, Ki-Ras, LUMAKRAS, lung, lung cancer, metastatic colon cancer gene testing, NGS, p.G12C, panitumumab, Ras, sotorasib, THOR, THORplex, Vectibix
    Components

    Interpretation

    Method

    Next-generation sequencing.

    The KRAS gene is sequenced and analyzed for mutations, including in KRAS codons 12, 13, 61, 117, and 146. This test can normally detect a heterozygous mutation if it is present in more than about 5% of the cells in the sample. This test was developed and its performance characteristics determined by the Department of Laboratory Medicine at the University of Washington.

    Reference Range
    See individual components
    Ref. Range Notes

    Results will be reported as either positive or negative for mutation.

    References
    • Skoulidis F, et al. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 384(25):2371-2381. PMID: 34096690
    • Karapetis CS, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008, 359:1757-65. 18946061
    • Lièvre A, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008, 26:374-9. 18202412
    • Also see correspondence for a good meta-analysis: J Clin Oncol 2008;26:2601-2602.
      Guidelines

      Ordering & Collection

      Specimen Type
      Tumor Tissue, Purified DNA, accompanied by a PATHOLOGY REPORT for the tested tissue.
      Collection

      Requirements for Specimen Selection

      • To ensure clinically relevant results, the most recent and/or metastatic sample is preferred to older specimens, provided sufficient tumor is present (see point 2).
      • To ensure detection of all types of mutations there should be at least 10% tumor cells in the tissue area processed for DNA for mutation detection and 20% tumor cells for microsatellite instability evaluation. If there is more than one tissue block, please provide the block that has the greatest percentage of neoplastic nuclei.
      • Tissue samples and pathology reports will be reviewed by directors upon receipt for acceptability prior to testing. Director consultation for tissue selection is available if needed (contact Genetics lab).

      Specimen Types

      Tissue samples

      Send one of the following:

      1. Slides: 1 slide at 4-micron thickness stained with hematoxylin-and-eosin (H&E) AND 10 unstained, non-baked slides at 10-micron thickness (a minimum of 5 unstained slides is acceptable). Unstained slides can be on charged or uncharged slides.
      2. Tissue Blocks: Provide complete formalin-fixed tissue block containing tumor tissue. Tissue block will be returned at completion of testing.
      3. Fresh/frozen tissue: 5 microgram tissue in cell culture medium or frozen tissue stored at -20C. Tumor percentage will not be determined prior to sequencing studies.

      NOTE: In order to ensure that enough DNA is obtained, the minimum acceptable tissue area is 10 square millimeters when ten 10-micron slides are supplied (1 cubic millimeter of tissue).

      Purified DNA

      5 micrograms ANDa reference hematoxylin-and-eosin (H&E) stained slide and pathology report required.

      Bone Marrow

      1 to 2 mL Bone Marrow in LAVENDER TOP (EDTA) tube

      Blood

      6 mL blood in LAVENDER TOP (EDTA) tube.

      Alternative specimens may be acceptable with approval (contact: 206-598-1149).

      For ADD-ON after prior testing, contact Genetics lab.

      Unacceptable samples

      We cannot accept decalcified samples or tissue samples treated with fixatives other than formalin.

      Quantity:

      Requested:

      • Tissue: 10 unstained slides (10-micron thickness) plus one H&E-stained slide.
      • Extracted DNA: 5 microgram Bone Marrow: 2 mL
      • Blood: 6 mL

      Minimum:

      • Tissue: 5 unstained slides (10-micron thickness) plus one H&E-stained slide.
      • Extracted DNA: 100-250 nanograms Bone Marrow: 1 mL
      • Blood: 3 mL
      Forms & Requisitions

      Genetics Requisition

      Providers with access to the UW implementation of Epic (i.e., FHCC, HMC, SCCA, UWMC, UWNW) may order this test using the order "UW Genetics and Solid Tumor Test Request." See tip sheet for more information (internal link).

      Handling Instructions

      Attach a copy of the pathology report for the tumor sample being submitted.

      Hold slides or tissue blocks at room temperature.

      Outside Laboratories: Ship at room temperature.

      Stability: unstained slides or tissue blocks stable at room temperature for at least 2 years

      Quantity
      requested: Amounts as noted above
      minimum: Amounts as noted above

      Processing

      Processing

      Performance

      LIS Dept Code
      Genetics (GEN)
      Performing Location(s)
      UW-MT Genetics

      Attention: Genetics Lab
      Clinical lab, Room NW220
      University of Washington Medical Center
      1959 NE Pacific Street
      Seattle, WA 98195

      Tel: 206-598–6429 M–F (7:30 AM–4:00 PM)
      Fax: 206-598–0304
      Lab email: cgateam@uw.edu

      Tel (EXOME only): 206-543-0459

      Manager
      Joe Bernal

      Genetic Counselors
      Angela Jacobson, MS, LGC
      Sandra Coe, MS,LGC
      Dru Leistritz, MS, LGC(EXOME testing only)

      Variant Review Scientist
      Ankita Jhuraney, PhD
      Sarah Paolucci, MA, MS, LGC
      Catherine A. Darcey, MSc
      Daniel W. Serber, PhD, MS, LCGC

      Faculty
      Jillian Buchan, PhD, FACMG
      Runjun Kumar, MD, PhD
      Christina Lockwood, PhD, DABCC, DABMGG
      Brian Shirts, MD, PhD
      Abbye McEwen, MD, PhD
      Colin Pritchard, MD, PhD
      Vera Paulson, MD, PhD
      Eric Konnick, MD, MS
      He Fang, PhD

      Frequency
      Run at least once a week; results within 2 weeks from specimen receipt
      Available STAT?
      No

      Billing & Coding

      CPT codes
      81275, 81276
      Billing Comments

      For pricing information, contact Client Support Services 206-520-4600 or 800-713-5198.

      LOINC
      21703-4
      Interfaced Order Code
      UOW2114