We performed a multicentric retrospective review of 12 patients treated between 1988 and 2018 for medulloblastoma with identified or highly suspected (personal of familial history) APC germline pathogenic variant.
Immunohistochemical detection of ALK protein identifies APC mutated medulloblastoma and differentiates the WNT-activated medulloblastoma from other types of posterior fossa childhood tumors.
In patients with FAP and identifiable APC gene mutation, CNS tumors, especially medulloblastoma which developed in most cases during childhood, are more common in females with FAP and APC gene mutation in codons 686-1217.
Germline mutations of APC in patients with Turcot syndrome (colon cancer and medulloblastoma), was well as somatic mutations of APC, beta-catenin, and Axin in sporadic medulloblastomas (MBs) have shown the importance of WNT signaling in the pathogenesis of MB.
A subset of cases is associated with colon cancer and APC germline mutations (Turcot syndrome), and APC and beta-catenin point mutations occur in up to 10% of sporadic cases, indicating the involvement of the Wnt pathway in the development of medulloblastoma.
Although medulloblastoma tumorigenesis has been associated strongly with FAP associated with APC germline mutation, none of the 22 informative sporadic cases revealed loss of heterozygosity of the APC gene locus.