Colorectal Cancer

Colorectal Cancer

Colorectal Cancer (CRC) Molecular Biomarkers

International guidelines recommend testing for hotspot mutations in the rat sarcoma viral oncogene homolog (RAS) gene family, including the Kirsten RAS (KRAS) and neuroblastoma RAS (NRAS) proto-oncogenes, to exclude RAS mutation-positive metastatic colorectal cancer (mCRC) patients from receiving anti-epidermal growth factor receptor (EGFR) therapy.

This is because anti-EGFR agents do not provide meaningful survival benefits versus anti-angiogenic/chemotherapy regimens in mCRC patients whose tumours are not wild type (WT) with respect to RAS genes1,2.

Mutations in proto-oncogene, KRAS, are detected in up to 40% of CRC patients. The activated KRAS gene contributes significantly to several aspects of the tumour growth, including tumour survival, angiogenesis, proliferation and metastasis. It is therefore vital that the KRAS mutation status of a patient’s colorectal tumour can be detected to allow patients access to treatment for which there is an increased likelihood of benefit3.

BRAF mutations occur in 15% of colorectal cancers. BRAF mutational status is used as a strong predictor for overall survival (OS) at all stages of disease; patients with BRAF-mutated CRC have a generally poor prognosis.

Traditionally, formalin-fixed paraffin-embedded (FFPE) tumour samples have been used to determine the RAS mutation status of CRC patients in routine clinical practice.

  • Somatic Mutation: Solid Tissue Molecular Profiling in Colorectal Cancer

    Somatic Mutation Brochure arrow icon   Somatic Mutation Request Form arrow icon

    Colorectal Cancer Solid Tissue Gene Panel

    Mutations in proto-oncogene KRAS are detected in up to 40% of CRC1, which can confer resistance to treatment with EGFR antibodies, and only patients with wild-type KRAS tumours obtain benefit from these agents2,3. It is, therefore, vital that the KRAS mutation status of a patient’s colorectal tumour can be detected to allow patients access to treatment.

    Genes sequenced in this panel include:

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    KRASPIK3CA
    NRASPTEN
    BRAFAKT1
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    How to Order Somatic Mutation Colorectal Cancer Gene Panel

    When to Order:

    • At diagnosis for treatment selection.

    Request Form Instructions:

    • Fill out our Somatic Mutation testing request form and tick the Somatic Mutation test panel required.

    Specimen Details:

    • Fresh formalin-fixed paraffin-embedded (FFPE) of 5-10 μm thickness from the tumour tissue.

    Test Cost:

    • Medicare rebate available if criteria is met. If criteria is not met there is an out-of-pocket fee of $400.

    Turnaround Time:

    • 5–7 business days from the sample receipt date.

    Notes:

    • A negative result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (<5%).


    References
    1. Bos JL et al., (1987) Nature 327(6120):293–297
    2. Van Cutsem E et al., (2009)     N Engl J Med 360(14):1408–1417.
    3. Bokemeyer C et al., (2009)     J Clin Oncol 27(5):663–671.

  • Aspect ctDNA Liquid Biopsy in Colorectal Cancer

    Aspect Liquid Biopsy Doctor Brochure arrow icon Aspect Liquid Biopsy Request Form arrow icon

    In colorectal cancer, ctDNA could also be used to track clonal evolution and targeted drug responses1,2.

    In patients with metastatic colorectal cancer who developed resistance to EGFR antibodies, analysis of ctDNA identified the emergence of polyclonal and heterogeneous patterns of mutation in KRAS, NRAS, BRAF, or EGFR with mutations found in 96% of panitumumab- or cetuximab refractory patients. Subsequently, Misale et al. were able to illustrate a way to use this information to overcome treatment resistance3,4,5.

    Furthermore, studies demonstrate better outcomes when no tumour-derived DNA is found in patients following surgery or chemotherapy in colorectal cancer patients, whereas those with whom tumour DNA is still present do better with the addition of more aggressive and targeted treatment or chemotherapy6.

    Colorectal Cancer ctDNA Gene Panel

    The Aspect Liquid Biopsy colorectal cancer (CRC) ctDNA gene panel can detect DNA alterations in patients’ plasma that guide treatment decisions as detailed below.

    Gene panel includes:

    • KRAS: 48 mutations across exon 2, 3 and 4
    • NRAS: 40 mutations across exon 2, 3 and 4
    • BRAF: 5 mutations across exon 11 and 15
    • PIK3CA: 4 mutations across exon 9 and 20
    • EGFR (T790M NOT included): 10 extracellular mutations across exon 12

    How to Order Aspect Liquid Biopsy

    When to Order:

    • For Lung Cancer & Melanoma: At diagnosis or on therapy for treatment selection.

    • For Colorectal Cancer: At diagnosis for treatment selection.

    Request Form Instructions:

    • Health practitioners can order Aspect Liquid Biopsy for cancer patients using the Aspect Liquid Biopsy form.

    • Patients can visit any of our convenient locations for their blood test. For locations, please visit our Locations page.

    Specimens Required:

    • This test requires TWO 10ml blood samples (special tubes).

    Test Cost:

    • No Medicare rebate available. An out-of-pocket fee of $550 applies.

    Turnaround Time:

    • 5–7 business days from the sample receipt date.

    Notes:

    • A negative result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (<2%).


    References:
    1. Gray E et al., (2015) Oncotarget 6 (39):42008–42018.
    2. Girotti M et al., (2016) Cancer Discov 6 (3):286–299.
    3. Bettegowda C et al., (2014) Sci Transl Med 6:224ra24.
    4. Misale S et al., (2012) Nature 486(7404):532–536.
    5. Misale S et al., (2014) Sci Transl Med 6:224ra26.
    6. Tie J et al., (2016) Sci Transl Med 8:346ra92.

References

  1. Bos JL et al., (1987) Nature 327(6120):293–297.
  2. Van Cutsem E et al., (2009) N Engl J Med 360(14):1408–1417
  3. Bokemeyer C et al., (2009) J Clin Oncol 27(5):663–671.

About the Author

Associate Professor Mirette Saad

Associate Professor Mirette Saad

MBBS(Hons) MD(Hons) MAACB FRCPA PhD

Associate Professor Mirette Saad

MBBS(Hons) MD(Hons) MAACB FRCPA PhD
Location: Clayton (VIC)
Speciality: Chemical Pathology
Areas of Interest:
  • antenatal screening
  • cancer genetics
  • clinical research and medical teaching
  • endocrine
  • fertility testing
  • molecular genetics
  • nipt
  • precision medicine
About

Associate Professor Mirette Saad is a Consultant Chemical Pathologist and the National Director of Molecular Genetics at Australian Clinical Labs. She has a Fellowship with honours in Chemical and Molecular Pathology, with Microbiology sub-speciality, from overseas. A/P Saad received her NHMRC sponsored PhD degree in Cancer Genetics from Melbourne University and Peter MacCallum Cancer Institute. Along with her teaching and research roles, A/P Saad is a registered medical practitioner with AHPRA, a Chemical Pathology Fellow (FRCPA) at the Royal College of Pathologists of Australasia and a Member of the Australasian Association of Clinical Biochemists (MAACB). She is a Chair of the RCPA Chemical Pathology Advisory Committee, Member of the RCPA Genetic Advisory Committee, AACB and a Chair of the Precision Medicine Services at Australian Clinical Labs. At Clinical Labs, A/Prof Mirette Saad leads the Molecular Genetic testing for NIPT, antenatal screening, personalised drug therapy and cancer.