Medulloblastoma Panel

Medulloblastoma is a primary central nervous system (CNS) malignant tumor that is more commonly observed in the pediatric population, as it affects approximately 9.6 children and 0.54 adults per million individuals (Smoll and Drummond. 2012. PubMed ID: 22981874). It is also more commonly reported in males than females (Khanna et al. 2017. PubMed ID: 28828582). The tumor starts in the brain at the base of the skull in the posterior fossa, and tends to spread to other areas of the brain and spinal cord. Individuals with medulloblastoma may experience issues with walking, balance, fine motor skills, headaches, nausea, seizures and other features. Treatment usually consists of surgery to remove as much tumor as possible and subsequent treatment by radiation and/or chemotherapy leading to improved prognosis and increased surveillance (Kameda-Smith. 2020. PubMed ID: 32095940).

Most cases of medulloblastoma are thought to be sporadic and have been stratified into molecular subgroups depending on the underlying biology and patient clinical characteristics (Juraschka and Taylor. 2019. PubMed ID: 31574483). These subgroups include wingless [WNT], sonic hedgehog [SHH], group 3, and group 4. However, there are also reports on the association of medulloblastoma in germline genetic disorders such as Gorlin syndrome, Li-Fraumeni syndrome, Fanconi anemia, familial adenomatous polyposis (FAP), and others. Genes associated with these disorders are tumor suppressors, and mutations in these genes are often loss of function sequence variants (e.g. premature protein termination); although missense and copy number variants have also been reported. Variants in these disorders can be inherited, but can also occur as de novo mutations. Pathogenic variants have also been observed in other germline genes that increase medulloblastoma risk. For instance, pathogenic variants in GPR161 have been reported to predispose individuals to pediatric medulloblastoma (Begemann et al. 2020. PubMed ID: 31609649). Germline loss of function variants in ELP1 have also been identified in individuals with medulloblastoma, especially pediatric patients in the SHH subgroup (Waszak et al. 2020. PubMed ID: 32296180).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.1% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Pathogenic variants in genes in this panel have been estimated to be responsible for approximately 5% of medulloblastoma diagnoses (Waszak et al. 2018. PubMed ID: 29753700).