Inherited Cancer Syndromes • Molecular Genetics Inherited Colon Cancer Panel

The Inherited Colon Cancer Panel is a multi-gene test that analyses genes associated with increased risk for colorectal cancer (CRC), the third most commonly diagnosed cancer in both men and women. In the United States, about 140,000 new cases of colorectal cancer are diagnosed each year. About 5 - 10% of all colorectal cancers are caused by a heritable mutation. 

The results from genetic tests can facilitate assessment of levels of risk for patients and lead to more efficient and appropriate medical management.  It is recommended that this testing be accompanied by a complete family history and genetic counseling.

Reasons for Referral:

• Confirmation of a clinical diagnosis of an inherited colon cancer.
• Testing for individuals with a positive family history for inherited colon cancer (targeted testing is available if familial mutation is known).

Genomic DNA is analyzed using next-generation sequencing (NGS) on the Illumina NextSeq 2000 platform, with target enrichment performed using hybridization-based probes to capture exonic (coding) regions of the gene(s). Single nucleotide variants (SNVs) and small insertions or deletions (INDELs) are identified using the Illumina DRAGEN Enrichment Workflow, executed onboard the NextSeq2000. This pipeline combines software and hardware acceleration to generate high-confidence germline haplotype calls. Clinical and analytical validation of DRAGEN was performed in our laboratory. Based on validation study results, for SNVs, this assay achieves >96% analytical sensitivity and >99% positive predictive value (PPV). For INDELs 87% and the PPV is >97%. INDELs >50 bp may be detected but the sensitivity for these is reduced. 

Exon-level copy number variants (CNVs) are detected using the Germline Copy Number Variation Best Practices pipeline from GATK. A Bayesian model, clinically validated in our laboratory, enables detection of deletions and duplications involving three or more contiguous exons in genes with adequate probe coverage and without complicating factors (e.g. pseudogene homology, short tandem repeats, segmental duplications). Please note that exon-centric microarray remains the gold standard for exonic copy number variant calling. If exon-centric microarray is of interest, please contact the laboratory for additional information. 

This test is not designed to detect polynucleotide repeats, low-level mosaicism, structural rearrangements or balanced alterations (e.g. inversions, gene conversion events, translocations, etc.) or variants in difficult regions. Additionally, variants located in regions of insufficient coverage, including introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and of high GC content may not be detected. This test does not provide complete coverage of all exons and noncoding regions may have limited information and ability to interpret. Variants in introns that are greater than 10 bp from the intron-exon junction may be analyzed. Please contact the laboratory if interrogation of intronic sequence greater than 10 bp from the intron-exon boundary is desired.

APC, EPCAM, GREM1, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1

Blood: EDTA or ACD (Solution A or B):

• Adult: 5 mL
• Child: 2-3mL
• Infant: 1-2mL

Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

DNA: 5-10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS).

For routine testing of blood and saliva (or DNA extracted from these specimens), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed within the above windows, please contact the laboratory.

Weekly

3-5 weeks

• Package and ship specimen to remain cold, but not frozen. 
• Ship via overnight express, using the FedEx priority overnight label provided. 
• Contact Client Services for shipping kits and instructions at (855) 535-1522.