Diagnostics

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Brain/Nervous System Cancer Panel

The Brain and Nervous System Cancer Panel is a comprehensive next-generation sequencing (NGS) panel that analyzes genes associated with increased risks for hereditary brain and nervous system cancer.

Brain and nervous system cancer affects approximately .6% of individuals in their lifetime (SEERP). Although the majority of brain and nervous system cancers are not related to heritable factors, approximately 5% of central nervous system cancers are associated with an underlying genetic etiology (Bleeker et al, 2014). Individuals who carry disease-causing genetic changes may be at significantly increased risk of developing brain or nervous system cancers in their lifetime; for example, individuals with pathogenic VHL variants have a 60-80% risk to develop hemangioblastoma (Wind and Lonser, 2011). Frequently, changes in genes that result in increased risks for brain and nervous system cancers also predispose individuals to increased risks for other malignancies.

Included Disorders

This panel includes genes associated with:

  • Constitutional mismatch repair deficiency syndrome
  • Costello syndrome
  • Cowden syndrome
  • Familial adenomatous polyposis
  • Li-Fraumeni syndrome
  • Multiple endocrine neoplasia type I
  • Nevoid basal cell carcinoma
  • Neurofibromatosis type 1
  • Neurofibromatosis type 2
  • Retinoblastoma
  • Tuberous sclerosis complex
  • von Hippel-Lindau syndrome

Inheritance

Hereditary brain and nervous system cancer is typically inherited an autosomal dominant fashion, although MLH1, MSH2, PMS2, and MSH6 are associated with autosomal recessive constitutional mismatch repair deficiency.

Indications for Testing

  • A personal history of brain or nervous cancer diagnosed at an early age
  • A personal history suggestive of one of the specific genetic syndromes included in this panel
  • 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 (35)

AIP ALK APC CDKN1B DICER1 EPCAM HRAS
MAX MEN1 MLH1 MSH2 MSH6 NF1 NF2
PHOX2B PMS2 PRKAR1A PTCH1 PTEN RB1 RET
SDHA SDHAF2 SDHB SDHC SDHD SMARCA4 SMARCB1
SMARCE1 SUFU TMEM127 TP53 TSC1 TSC2 VHL

Additions to the Brain/Nervous System Cancer Panel:

Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with hereditary brain and nervous system cancer, but emerging evidence suggests that they may play a role in disease pathogenesis.

Emerging Evidence (3):

BAP1 BARD1 EZH2 GPC3 KIF1B POT1 PTCH2

References:

  • Bleeker FE, Hopman SM, Merks JH, Aalfs CM, Hennekam RC. Brain tumors and syndromes in children. Neuropediatrics. 2014;45(3):137-61.
  • Surveillance, Epidemiology, and End Results Program (SEERP). Cancer Stat Fact Sheets [Accessed April 20, 2017]. Available from: http://seer.cancer.gov/
  • Wind JJ, Lonser RR. Management of von Hippel-Lindau disease-associated CNS lesions. Expert Rev Neurother. 2011;11(10):1433-41.