Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas

Priscilla K. Brastianos, Amaro Taylor-Weiner, Peter E. Manley, Robert T. Jones, Dora Dias-Santagata, Aaron R. Thorner, Michael S. Lawrence, Fausto J. Rodriguez, Lindsay A. Bernardo, Laura Schubert, Ashwini Sunkavalli, Nick Shillingford, Monica L. Calicchio, Hart G.W. Lidov, Hala Taha, Maria Martinez-Lage, Mariarita Santi, Phillip B. Storm, John Y.K. Lee, James N. PalmerNithin D. Adappa, R. Michael Scott, Ian F. Dunn, Edward R. Laws, Chip Stewart, Keith L. Ligon, Mai P. Hoang, Paul Van Hummelen, William C. Hahn, David N. Louis, Adam C. Resnick, Mark W. Kieran, Gad Getz, Sandro Santagata

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)161-165
Number of pages5
JournalNature genetics
Volume46
Issue number2
DOIs
StatePublished - Feb 2014

ASJC Scopus subject areas

  • Genetics

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    Brastianos, P. K., Taylor-Weiner, A., Manley, P. E., Jones, R. T., Dias-Santagata, D., Thorner, A. R., Lawrence, M. S., Rodriguez, F. J., Bernardo, L. A., Schubert, L., Sunkavalli, A., Shillingford, N., Calicchio, M. L., Lidov, H. G. W., Taha, H., Martinez-Lage, M., Santi, M., Storm, P. B., Lee, J. Y. K., ... Santagata, S. (2014). Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nature genetics, 46(2), 161-165. https://doi.org/10.1038/ng.2868