Sema4 Signal Hereditary Cancer Lynch Syndrome Panel

Related Gene(s): MLH1, MSH2, MSH6, PMS2, EPCAM

Lynch Syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is characterized by an increased risk for colorectal cancer and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain and skin.

Test description/technology:

The Lynch Syndrome Panel analyzes 5 genes (listed above) by next generation sequencing (NGS). This test detects variants within the exons and the intron-exon boundaries of the target regions. Variants outside these regions are not reported unless they are clinically significant. Most regions not meeting a minimum of >20X read depth across the exon are further analyzed by Sanger sequencing. Copy Number Variant (CNV) analysis is performed by relative depth analysis of NGS data. In addition, CNVs in EPCAM, MLH1, MSH2, MSH6 and PMS2 are analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA). Analysis of EPCAM is limited to CNVs deletion/duplication analysis. Variants are classified using the ACMG/AMP framework and variants classified as uncertain significance, likely pathogenic, pathogenic are confirmed using an alternate technology (SNVs and indels: Sanger sequencing, CNVs: qPCR, MLPA or ddPCR). PMS2 variants are confirmed by long-range PCR. The inversion of coding exons 1-7 of the MSH2 gene is detected by NGS and MLPA. This test has an analytic sensitivity of >99 % (SNVs and small indels) and 89 % (CNVs). This test has not been validated to reliably detect certain variant types including mosaic variants, variants located within repeat expansions or structural genomic variation.

Single gene testing is available.  In addition, known familial variant testing can be ordered (please include a copy of the family member’s test report with the requisition form).


Turnaround Time

  • 14-21 days from receipt of specimen

Specimen Requirements

  • Whole blood samples: 2 lavender-top (EDTA) tubes, 5-10 mL of blood from the patient are required.
  • Extracted DNA samples: We request 20 µL DNA (50-250 ng/µL) or at minimum require 10 µL DNA (50-250 ng/µL). Causes for rejection include impurities in the test or reference DNA samples, including NaCl or KCl (>40 mM) and other salts, phenol, ethanol, heparin, EDTA (>1.5 mM), and Fe, contaminated DNA, and low concentration of DNA (<20 ng/µL).
  • Saliva samples: Saliva samples should be collected in Oragene DNA (OG-500) kits by DNA Genotek.
  • Cheek swab: 1 Isohelix(SK-1) cheek swab specimen from the patient is required.

Tubes of blood should be kept and shipped refrigerated or at room temperature (PLEASE DO NOT FREEZE).


Related Tests


Resources

Hereditary Cancer Requisition
Hereditary Cancer Re-Requisition
Hereditary Cancer Genetic Testing Consent
Hereditary Cancer Provider Brochure