Do Craniopharyngioma Molecular Signatures Correlate with Clinical Characteristics?

Introduction: Exome sequencing studies have recently demonstrated that papillary (C-PAP) and adamantinomatous craniopharyngiomas (aCP) have distinct genetic origins, each primarily driven by mutually exclusive alterations either BRAF (V600 E), observed in 95% of C-PAP or CTNNB1, observed in 75 - 96% of aCP. How these molecular signatures, or their absence, correlate with clinical, radiographic and outcome variables is unknown.

Methods: The pathology records were reviewed from May 2000 to March 2015 at Weill Cornell Medical College and craniopharyngiomas were identified and classified as C-PAP or aCP. Patients were grouped under 3 genomic mutation types: BRAF mutation only, CTNNB1 mutation only, tumors with none of these mutations detected (Not Detected). Demographic data, presenting symptoms, age, extent of resection, recurrence were correlated with genetic mutations.

Results: Histology correlated strongly with mutation group. All BRAF mutated tumors were C-PAP, All CTNNB1 and all Not Detected tumors were aCP. Pre- and post-operative clinical symptoms and radiographic features did not correlate with any mutation group. However, patients with no mutations (Not Detected) were more likely to be pediatric (p = 0.022) and have tumors in the sella (p = 0.008). Extent of resection complications and recurrence did not correlate with mutation group.

Conclusion: Craniopharyngioma mutation signature is highly predictive of histology. The subgroup of tumors with no detected mutations are more likely pediatric, located in the sella and of aCP histology.