Do craniopharyngioma molecular signatures correlate with clinical characteristics?
OBJECTIVE Exome sequencing studies have recently demonstrated that papillary craniopharyngiomas (PCPs) and adamantinomatous craniopharyngiomas (ACPs) have distinct genetic origins, each primarily driven by mutually exclusive alterations: either BRAF ( V600E), observed in 95% of PCPs, or CTNNB1, observed in 75%-96% of ACPs. How the presence of these molecular signatures, or their absence, correlates with clinical, radiographic, and outcome variables is unknown. METHODS The pathology records for patients who underwent surgery for craniopharyngiomas between May 2000 and March 2015 at Weill Cornell Medical College were reviewed. Craniopharyngiomas were identified and classified as PCP or ACP. Patients were placed into 1 of 3 groups based on their genomic mutations: BRAF mutation only, CTNNB1 mutation only, and tumors with neither of these mutations detected (not detected [ND]). Demographic, radiological, and clinical variables were collected, and their correlation with each genomic group was tested. RESULTS Histology correlated strongly with mutation group. All BRAF tumors with mutations were PCPs, and all CTNNB1 with mutations and ND tumors were ACPs. Preoperative and postoperative clinical symptoms and radiographic features did not correlate with any mutation group. There was a statistically significant relationship (p = 0.0323) between the age group (pediatric vs adult) and the mutation groups. The ND group tumors were more likely to involve the sella (p = 0.0065). CONCLUSIONS The mutation signature in craniopharyngioma is highly predictive of histology. The subgroup of tumors in which these 2 mutations are not detected is more likely to occur in children, be located in the sella, and be of ACP histology.
['Omay|Sacit Bulent|SB|', 'Chen|Yu-Ning|YN|', 'Almeida|Joao Paulo|JP|', 'Ruiz-Treviño|Armando Saul|AS|', 'Boockvar|John A|JA|', 'Stieg|Philip E|PE|', 'Greenfield|Jeffrey P|JP|', 'Souweidane|Mark M|MM|', 'Kacker|Ashutosh|A|', 'Pisapia|David J|DJ|', 'Anand|Vijay K|VK|', 'Schwartz|Theodore H|TH|']
D000293:Adolescent D000328:Adult D000367:Age Factors D000368:Aged D000369:Aged, 80 and over D014408:Biomarkers, Tumor D001932:Brain Neoplasms D002648:Child D002675:Child, Preschool D003397:Craniopharyngioma D005260:Female D005500:Follow-Up Studies D006801:Humans D008297:Male D008875:Middle Aged D009154:Mutation D009364:Neoplasm Recurrence, Local D048493:Proto-Oncogene Proteins B-raf D047368:Tumor Burden D055815:Young Adult D051176:beta Catenin
craniopharyngioma papillary adamantinomatous BRAF CTNNB1 ACP = adamantinomatous craniopharyngioma DI = diabetes insipidus GTR = gross-total resection ND = not detected PCP = papillary craniopharyngioma pituitary surgery