OncologyInherited Cancer Syndromes

The vast experience of Knight Diagnostic Laboratories in the fields of genetics and molecular pathology combine in the diagnosis of inherited cancer syndromes. While most cancer is random, 5-10% of all cancers are associated with mutations in susceptibility genes that have been genetically transmitted from parent to child, often through several generations. Understanding the molecular etiology of such cancers not only guides treatment and surveillance, but may have significant impact on other family members as well. 

Oregon Health & Science University is a center of excellence for diagnosis and treatment of Fanconi anemia, a recessively inherited chromosome instability syndrome. Knight Diagnostic Laboratories has been providing comprehensive molecular analyses of the Fanconi genes and other disorders for many years. 

Until recently, testing for inherited cancer syndrome genes was accomplished using Sanger sequencing (for DNA base-level changes) and multiplex ligation-dependent probe amplification (for exon-level deletions and duplications). Recently, we have transitioned to next-generation sequencing for detection of sequence-level changes and exon-level chromosomal microarray for detection of exonic deletions and duplications.   Our next-generation sequencing Inherited Cancer Panel 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. 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 cancer-associated syndromes associated with single gene defects, such as Birt-Hogg-Dube, Bloom, Gorlin, Li-Fraumeni and vonHippel-Lindau, among others.

Reasons for Referral include confirmation of a clinical diagnosis of an inherited cancer and testing for individuals with a positive family history for inherited cancer (targeted testing is available if familial mutation is known).

All inherited cancer syndrome testing is performed and interpreted as described for genetic rare disorders by American College of Medical Genetics. It is recommended that this testing be accompanied by a complete family history and genetic counseling.

Key syndromes studied at our laboratories include:

• Fanconi anemia ( FANCA, FANCC,FANCG, FANCF, FANCE)
• Lynch syndrome (MLH1, MSH2, MSH6, PMS2),
• Familial adenomatous polyposis (APC),
• Multiple endocrine neoplasia (RET),
• von Hippel-Lindau disease (VHL).