Medulloblastoma Subgroups and the Role of WNT signaling Mutations in CTNNB1 and APC Genes

Explore the classification of Medulloblastoma into four subgroups and understand the impact of CTNNB1 and APC gene mutations driving constitutive WNT signaling in the context.

 

Medulloblastoma Subtypes: Wnt Signaling Mutaions in CTNNB1 and APC genes

We know that Medulloblastoma was divided into four subgroups: WNT, SHH, Group3, and Group4. In the context of molecular mutations, the somatic CTNNB1 mutations or germline APC mutations drive constitutive WNT signaling. And then, we know the mutation sites of CTNNB1 or APC gene.

 

Mutaion sites of CTNNB1 or APC gene and abnormal regulation of it

In medulloblastoma with WNT signaling activation, somatic CTNNB1 mutations are commonly found in exon 3. These mutaions often target specific serine or threonine residues, such as Ser33,  Ser37, Thr41, and Ser45, which are involved in the regulation of beta-catenin stability. When these residues are mutated, beta-catenin degradation is prevented, leading to the accumulation of beta-catenin and constitutive activation of WNT signaling.

 

Germline APC mutations, associated with familial adenomatous polyposis (FAP), can also contribute to medulloblastoma. APC is a tumor suppressor gene located on chromosome 5q21-22. Mutation in this gene result in truncated APC proteins that are unable to regulate beta-catenin, leading to the activation of WNT signaling and an increased risk of tumor development.