Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation
- 540 Downloads
Initially described in 2011, it is now recognized that medulloblastomas (MB) can be stratified into four distinct molecular subgroups (WNT-activated, SHH-activated, Group 3, and Group 4) on the basis of underlying genetic alterations, transcriptional profiles, or genome-wide DNA methylation patterns that more accurately predict clinical outcomes than histologic features alone [4, 7]. The recurrent genetic alterations that characterize each of these four molecular subgroups have been described over the last few years [2, 5, 6, 8, 9]. WNT-activated MB, associated with favorable prognosis, are genetically defined by activating mutations in CTNNB1 (encoding beta-catenin) often accompanied by monosomy 6 and alterations in chromatin regulatory genes. SHH-activated MB, associated with intermediate or poor prognosis depending on the status of the TP53 tumor suppressor gene, are genetically characterized by alterations in components of the sonic hedgehog (SHH) signaling pathway including PTCH1,...
J.B.I. is supported by the Arthur Purdy Stout Stipend Award. B.C.B. is supported by an NCI Outstanding Investigator Award (R35 CA220481). D.A.S. is supported by NIH Director’s Early Independence Award (DP5 OD021403).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests related to this report.