title: Genomic Alterations of Adamantinomatous and Papillary Craniopharyngioma.
abstract: Craniopharyngiomas are rare histologically benign but clinically challenging neoplasms. To obtain further information on the molecular genetics and biology of craniopharyngiomas, we analyzed a cohort of 121 adamantinomatous and 16 papillary craniopharyngiomas (ACP, PCP). We extracted DNA from formalin-fixed paraffin-embedded tissue and determined mutational status of CTNNB1, BRAF, and DDX3X by Sanger sequencing, next generation panel sequencing, and pyrosequencing. Sixteen craniopharyngiomas were further analyzed by molecular inversion profiling (MIP); 76.1% of the ACP were mutated in exon 3 of CTNNB1 encoding for β-catenin and there was a trend towards a worse event-free survival in cases mutated at Thr41. Next generation panel sequencing of 26 ACP did not detect any recurrent mutations other than CTNNB1 mutations. BRAF V600E mutations were found in 94% of the PCP, but not in ACP. GISTIC analysis of MIP data showed no significant larger chromosomal aberrations but a fraction of ACP showed recurrent focal gains of chromosomal material, other cases showed loss in the chromosomal region Xq28, and a third group and the PCP had stable genomes. In conclusion, the crucial pathogenetic event appears to be WNT activation in ACP, whereas it appears to be activation of the Ras/Raf/MEK/ERK pathway by BRAF V600E mutations in PCP.
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Goschzik
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Dreschmann
authors.affiliation: Department of Pediatrics, Klinikum Oldenburg AöR, Medical Campus University Oldenburg, Oldenburg, Germany.
authors.forename: Ursel
authors.initials: U
authors.lastname: Gebhardt
authors.affiliation: Human Genome Sequencing Center, Department of Molecular and Human Genetics, Houston, Texas, USA.
authors.forename: Linghua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Human Genome Sequencing Center, Department of Molecular and Human Genetics, Houston, Texas, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Department of Anatomic Pathology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ching C
authors.initials: CC
authors.lastname: Lau
authors.affiliation: Department of Pediatrics, Klinikum Oldenburg AöR, Medical Campus University Oldenburg, Oldenburg, Germany.
authors.forename: Hermann L
authors.initials: HL
authors.lastname: Müller
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D003397:Craniopharyngioma / Q000235:genetics* / Q000473:pathology*; D005260:Female; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
keywords: Chromosomal aberrations; Craniopharyngioma; Mutation analysis; β-Catenin; WNT signaling