• Test Code:
    2025
  • Department:
    Molecular Genetics
  • Test Synonyms:
    Familial CancerHereditary CancerBreast CancerOvarian CancerEndometrial CancerColon CancerColorectal cancerLynch SyndromeRenal CancerPancreatic CancerMultiple Endocrine NeoplasiaMelanomaBirt-Hogg-DubeBloomCarney ComplexGorlin SyndromeAPCATMBAP1BARD1BLMBMPR1ABRCA1BRCA2BRIP1CDC73CDH1CDK4CDKN1BCDKN2ACHEK2EPCAMFHFLCNMAXMEN1METMITFMLH1MRE11AMSH2MSH6MUTYHNBNNF1PALB2PMS2PRKAR1APTCH1PTENRAD50RAD51CRAD51DRB1RETSDHASDHAF2SDHBSDHCSDHDSMAD4STK11TMEM127TP53TSC1TSC2VHLXRCC2
  • CPT Code(s):
    8132381404x581405x581406x481407814088143281433814358143681479
Background:

A fraction of all cancers are associated mutations in susceptibility genes that have been genetically transmitted, often through several generations.  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 52 genes associated with cancer, or increasing the risk for cancer onset. Our microarray test is designed to identify single exon deletions and duplications in the same 52 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. This set of genes includes genes associated with: breast/ovarian/endometrial cancers; GI cancers, such as Lynch syndrome; renal and pancreatic cancers; melanoma; endocrine tumors, including multiple endrocrine neoplasia; and syndromes associated with single gene defects, such as Birt-Hogg-Dube, Bloom, Gorlin, Li-Fraumeni and Von-Hippel-Lindau, among others.  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 cancer.
  • Testing for individuals with a positive family history for inherited cancer (targeted testing is available if familial mutation is known)

Methodology:

This test has two components:
Component 1: Next generation sequencing will analyze the exons or coding regions of 52 inherited cancer-associated genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions.

Any gaps in coverage in clinically validated genes are completed with traditional Sanger sequencing such that 100% of the coding region of the above genes are covered at 10x coverage or more.  Promoter, intronic, etc. regions are not assessed here but may contain variants that impact gene function.

Component 2: Deletion/Duplication Analysis – A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications. The targeted array has enhanced probes targeted to the exonic regions of the 52 inherited cancer-associated genes medically relevant genes. The arrays will be run using Agilent SureScan technology. This array is an ideal complement to the next generation sequencing approach to provide a comprehensive mutation spectrum analysis for inherited cancer.

The 52 inherited cancer-associated genes are listed below:
Comprehensive Inherited Cancer (52 genes)
APC, ATM, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CDC73, CDH1, CDK4, CDKN1B, CDKN2A, CHEK2, EPCAM, FH, FLCN, MAX, MEN1, MET, MITF, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PRKAR1A, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RB1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, STK11, TMEM127, TP53, TSC1, TSC2, VHL, XRCC2

Specimen Requirements:

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

  • Adult: 5 mL

 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:

Specificity and Sensitivity:
Specificity = 100%
Sensitivity = 97%