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Nat Genet DOI:10.1038/ng.2868

Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas.

Publication TypeJournal Article
Year of Publication2014
AuthorsBrastianos, PK, Taylor-Weiner, A, Manley, PE, Jones, RT, Dias-Santagata, D, Thorner, AR, Lawrence, MS, Rodriguez, FJ, Bernardo, LA, Schubert, L, Sunkavalli, A, Shillingford, N, Calicchio, ML, Lidov, HGW, Taha, H, Martinez-Lage, M, Santi, M, Storm, PB, Lee, JYK, Palmer, JN, Adappa, ND, R Scott, M, Dunn, IF, Laws, ER, Stewart, C, Ligon, KL, Hoang, MP, Van Hummelen, P, Hahn, WC, Louis, DN, Resnick, AC, Kieran, MW, Getz, G, Santagata, S
JournalNat Genet
Date Published2014 Feb
KeywordsBase Sequence, Bayes Theorem, beta Catenin, Craniopharyngioma, Exome, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, Molecular Sequence Data, Mutation, Missense, Pituitary Neoplasms, Proto-Oncogene Proteins B-raf, Sequence Analysis, DNA

Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (β-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms.


Alternate JournalNat. Genet.
PubMed ID24413733
PubMed Central IDPMC3982316
Grant ListK08 NS064168 / NS / NINDS NIH HHS / United States
K12 CA090354 / CA / NCI NIH HHS / United States
P01 CA142536 / CA / NCI NIH HHS / United States
K12 CA090354-11 / CA / NCI NIH HHS / United States