Background:
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.
Understanding the molecular etiology of such cancer incidence can help guide treatment and proper surveillance. Our next-generation sequencing test is designed to detect mutations in the coding region of 9 genes associated with inherited colon cancer, or increasing the risk for cancer onset. Our microarray test is designed to identify single exon deletions and duplications in the same 9 inherited colon cancer-associated genes. Combining deletion/duplication data analyzed by microarray with next generation sequencing data will allow KDL to improve diagnostic yield and deliver more comprehensive results.
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).
Methodology:
Next generation sequencing (NGS) will analyze the exons or coding regions of 9 inherited colon cancer-associated genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions. This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.
Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version 4.1.4.1. A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.
The 9 inherited colon cancer-associated genes are listed below:
APC, EPCAM, GREM1, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1
Specimen Requirements:
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.
Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks.
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).
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.
Test Performed (Days):
Weekly
Turn Around Time:
3 weeks
Shipment Sensitivity Requirements:
- 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.
References:
Additional Info: