Diagnostics

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Pancreatic Cancer Panel

The Pancreatic Cancer Panel is a comprehensive next-generation sequencing (NGS) panel that analyzes genes associated with increased risks for hereditary pancreatic cancer.

Pancreatic cancer affects approximately 1.5% of individuals in their lifetime (SEERP). Although the majority of pancreatic cancer is not related to heritable factors, in approximately 5-10% cases pancreatic cancer may be hereditary (Shi et al, 2009). Individuals who carry disease causing genetic changes may be at significantly increased risk of developing pancreatic cancer in their lifetime. For example, individuals with a pathogenic BRCA1/2 mutation have up to 7% lifetime risk for pancreatic cancer (Petrucelli et al,1998), while individuals with STK11 or CDKN2A mutations have up to 36% and 17% lifetime risks for pancreatic cancer, respectively (van Lier et al, 2010; Vasen et al, 2000). Frequently, changes in genes that result in increased risks for pancreatic cancer also predispose individuals to increased risks for other malignancies.

Included Disorders

This panel includes genes associated with:

  • Familial adenomatosis polyposis
  • Hereditary breast and ovarian cancer syndrome
  • Juvenile polyposis syndrome
  • Li-Fraumeni syndrome
  • Lynch syndrome (hereditary non-polyposis colorectal cancer)
  • Melanoma-pancreatic cancer syndrome
  • Multiple endocrine neoplasia type 1
  • Neurofibromatosis type 1
  • Peutz-Jeghers syndrome
  • Tuberous sclerosis complex
  • von Hippel-Lindau syndrome
  • Hereditary pancreatitis

Inheritance

Hereditary pancreatic cancer is typically inherited in an autosomal dominant manner, although several of the genes on this panel are associated with recessive genetic conditions:

  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency
  • ATM is associated with ataxia telangiectasia
  • BRCA2 and PALB2 are associated with Fanconi anemia

Indications for Testing

  • A personal history of early pancreatic 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 (20)

APC ATM BMPR1A BRCA1 BRCA2 CDKN2A EPCAM MEN1 MLH1 MSH2
MSH6 NF1 PALB2 PMS2 SMAD4 STK11 TP53 TSC1 TSC2 VHL

Additions to the Pancreatic Cancer Panel:

Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with hereditary pancreatic cancer, but emerging evidence suggests that they may play a role in disease pathogenesis. Genes related to hereditary chronic pancreatitis can also be added to the comprehensive panel. Chronic pancreatitis may cause increased risks for pancreatic cancer in some individuals.

Emerging Evidence (3):

CDK4 FANCC PALLD

Chronic Pancreatitis Genes (5):

CASR CFTR CTRC PRSS1 SPINK1

References:

  • Chanjuan Shi, Ralph H. Hruban, and Alison P. Klein (2009) Familial Pancreatic Cancer. Archives of Pathology & Laboratory Medicine: March 2009, Vol. 133, No. 3, pp. 365-374.
  • Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2016 Dec 15]. 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/NBK1247/
  • Surveillance, Epidemiology, and End Results Program (SEERP). Cancer Stat Fact Sheets [Accessed April 20, 2017]. Available from: http://seer.cancer.gov/
  • Van lier MG, Wagner A, Mathus-vliegen EM, Kuipers EJ, Steyerberg EW, Van leerdam ME. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105(6):1258-64.
  • Vasen HF, Gruis NA, Frants RR, Van der velden PA, Hille ET, Bergman W. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000;87(6):809-11.