Diagnostics

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Renal/Urinary Tract Cancer Panel

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.

Included Disorders

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

Inheritance

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

Methodology

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)

BAP1 CDC73 CDKN1C DICER1 DIS3L2 EPCAM FH FLCN GPC3
MET MITF MLH1 MSH2 MSH6 PMS2 PTEN SDHA SDHB
SDHC SDHD SMARCA4 SMARCB1 TP53 TSC1 TSC2 VHL WT1

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):

BUB1B CEP57 PALB2

References:

  • 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/