The Renal/Urinary Tract Cancer Panel is a comprehensive next-generation sequencing (NGS) panel that analyzes genes associated with increased risks for hereditary renal cancer.
Renal cancer affects approximately 1.6%, and bladder cancer 2.6% of individuals in their lifetime (SEERP). Although the majority of renal and urinary tract malignancies are not related to heritable factors, approximately 3-5% of renal cell carcinoma cases are due to genetic changes (Coleman and Russo, 2009). Individuals who carry disease-causing genetic changes may be at significantly increased risk of developing renal or urinary tract tumors in their lifetime. For example, individuals with a pathogenic VHL variant have up to a 70% risk for renal cancer (Frantzen et al, 2000; Houweling et al, 2011). Frequently, changes in genes that result in increased risks for renal/urinary cancers also predispose individuals to increased risks for other malignancies.
This panel includes genes associated with:
- Lynch syndrome (hereditary non-polyposis colon cancer)
- Birt-Hogg-Dubé syndrome
- Cowden syndrome
- Li-Fraumeni syndrome
- Tuberous sclerosis complex
- von Hippel-Lindau syndrome
- Hereditary leiomyomatosis and renal cell carcinoma
- Perlman syndrome
- Simpson-Golabi-Behmel syndrome
- Hereditary paragangliomas and pheochromocytoma
Hereditary renal and urinary tract cancer is typically inherited in an autosomal dominant manner, although GPC3 is inherited in an X-linked fashion and MLH1, MSH2, PMS2, and MSH6 are associated with autosomal recessive constitutional mismatch repair deficiency.
Indications for Testing
- A personal history of early renal cancer
- A personal history of early urinary tract cancer
- A personal history of multiple primary cancers
- A family history suggestive of a hereditary cancer syndrome, including multiple individuals on the same side of a family diagnosed with cancer, especially at ages below population averages
- Risk assessment for asymptomatic family of members of proband with molecular diagnosis of a hereditary cancer syndrome
Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering.
Included Genes (27)
Additions to the Renal/Urinary Tract Cancer Panel:
Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with hereditary renal and urinary tract cancer, but emerging evidence suggests that they may play a role in disease pathogenesis.
Emerging Evidence (3):
- Coleman JA, Russo P. Hereditary and familial kidney cancer. Curr Opin Urol. 2009;19(5):478-85.
- Houweling AC, Gijezen LM, Jonker MA, et al. Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. Br J Cancer. 2011;105(12):1912-9.
- Frantzen C, Klasson TD, Links TP, et al. Von Hippel-Lindau Syndrome. 2000 May 17 [Updated 2015 Aug 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1463/
- Surveillance, Epidemiology, and End Results Program (SEERP). Cancer Stat Fact Sheets [Accessed April 20, 2017]. Available from: http://seer.cancer.gov/