Colorectal cancer

Colorectal cancer is cancer that starts in the colon or the rectum. The major histologic subtype of colorectal cancer is adenocarcinoma which arise through acquisition of a series of mutations in different genes (as shown in the pie chart). These genes serve as a prognostic or predictive marker for targeted therapies available in colorectal cancer[1].


Molecular Subtype in Colorectal Adenocarcinoma


The targeted agents (anti-EGFR monoclonal antibodies cetuximab and panitumumab) alone or in combination with chemotherapy are current standard of treatment for metastatic colorectal cancer. However, tumours harbouring mutations in KRAS, NRAS and BRAF are unlikely to respond to this anti-EGFR antibody therapy. These mutations were suggested to be a negative predictor of response to anti-EGFR therapy. Therefore, NCCN guideline recommends testing of KRAS, NRAS and BRAF mutations in patients with metastatic colorectal cancer prior to the use of EGFR antibody agents cetuximab and panitumumab[2-5].

Oncode offers range of next-generation sequencing (NGS) panels for colorectal cancer from smaller panel like Colon LiquidPinpoint panel to comprehensive panels.

ONCODEcipher Colon LiquidPinpoint
ONCODEcipher Colon LiquidPinpoint is a NGS panel targeting 5 most important genes that are frequently mutated in colon cancer, given as KRAS, NRAS, BRAF, EGFR and ALK using only the blood of the patients.

Specimen Requirements:
15ml blood in Streck tubes

Turn Around Time:
10 working days

Shipment Requirement:
Keep specimen at room temperature. DO NOT ship on ice or dry ice or expose to direct sunlight.
ONCODEcipher Colon Liquid28
ONCODEcipher Colon Liquid28 is a NGS panel that delivers information on a variety of treatment-informative mutations in the 28 genes which are known to play a role in cases of colorectal cancer using only the blood of the patients.

Specimen Requirements:
15ml blood in Streck tubes

Turn Around Time:
10 working days

Shipment Requirement:
Keep specimen at room temperature. DO NOT ship on ice or dry ice or expose to direct sunlight.
ONCODEcipher Colon Comprehensive
ONCODEcipher Colon Comprehensive is a targeted NGS panel that simultaneously detects and characterizes single nucleotide polymorphisms (SNVs) and insertions and deletions (indels) in 67 genes associated with solid tumours.

Specimen Requirements:
• FFPE block OR 10 FFPE Slides (10µm thick sections) with at least 30% tumour cellularity
• 1 H&E stained slide cut from same block

Turn Around Time:
10 working days

Shipment Requirement:
Keep specimen at room temperature. DO NOT ship on ice or dry ice or expose to direct sunlight.
ONCODEcipher MSI
Microsatellites are short, tandemly repeated DNA sequences from 1-6 base pairs in length. Microsatellite markers can be used to detect a form of genetic instability called Microsatellite Instability (MSI). MSI is a consequence of germline or somatic inactivation of mismatch repair (MMR) deficient. Loss or down-regulation of the expression of the protein products of these genes results in failure of the DNA mismatch repair system.

NCCN guideline recommends testing all patients with colorectal cancer for Lynch syndrome also known as Hereditary non-polyposis colorectal cancer (HNPCC) for better treatment planning. MSI occurs in more than 90% of patients with Lynch syndrome. MSI can also occur in the absence of Lynch syndrome as they are found in about 15% of colon cancers without Lynch syndrome. Family members who are at risk of inherited the familial mutation of Lynch syndrome can be tested to determine whether they are at risk for developing colorectal cancer and if so, they should undergo frequent surveillance screening[1].

Earlier studies have suggested that metastatic colorectal cancer patients with high levels of MSI indicates a better prognosis and is more sensitive to immunotherapy (pembrolizumab). Recent studies have shown that MSI is also a useful indicator for predicting response to immunotherapy in any solid tumour type[2].

ONCODEcipher MSI test is a PCR and fragment analysis assay to detect the increase in length of the microsatellite segment by comparing microsatellite allele size variations between normal and tumour samples in five mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27) and two pentanucleotide repeat marker (Penta C and Penta D).

Specimen Requirements:
Tumour FFPE block OR 10 FFPE Slides (10µm thick sections) with at least 30% tumour cellularity & 1 H&E stained slide cut from same block AND
Non-Tumour 3ml blood in EDTA tube OR FFPE Block OR 10 unstained Slides (10µm thick sections) of non-tumour tissue

Turn Around Time:
10 working days

Shipment Requirement:
Keep specimen at room temperature. DO NOT ship on ice or dry ice or expose to direct sunlight.
References:
1. Chan, E. (2016). Molecular Profiling of Colorectal Cancer. My Cancer Genome. READ MORE.
2. De Roock, W., Biesmans, B., De Schutter, J. & Teipar, S. (2009). Clinical Biomarkers in Oncology: Focus On Colorectal Cancer. Molecular Diagnosis & Therapy 13(2): 103-14.
3. National Comprehensive Cancer Network (2017). Colon Cancer. NCCN Guidelines for Patients. READ MORE
4. Punt, C.J, Koopman, M. & Vermeulen, L. (2017). From Tumour Heterogeneity to Advances in Precision Treatment of Colorectal Cancer. Nature Reviews Clinical Oncology 14(4):235-246. doi: 10.1038/nrclinonc.2016.171.
5. Rizzo, S. et. al. (2010). Prognostic vs Predictive Molecular Biomarkers in Colorectal Cancer: is KRAS and BRAF Wild Type Status Required for Anti-EGFR Therapy? Cancer Treatment Reviews 36 Suppl 3: S56-61.