Format

Send to

Choose Destination
Nat Genet. 2014 Feb;46(2):161-5. doi: 10.1038/ng.2868. Epub 2014 Jan 12.

Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas.

Author information

1
1] Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Division of Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [5] Broad Institute of MIT and Harvard, Boston, Massachusetts, USA. [6].
2
1] Broad Institute of MIT and Harvard, Boston, Massachusetts, USA. [2].
3
1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2].
4
1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
5
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
6
Broad Institute of MIT and Harvard, Boston, Massachusetts, USA.
7
Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
8
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
9
Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
10
Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
11
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA. [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
12
Children's Cancer Hospital Egypt, Cairo, Egypt.
13
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
14
Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
15
1] Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2] Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
16
Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
17
1] Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2] Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
18
Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
19
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts, USA.
20
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
21
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA. [4] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
22
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Broad Institute of MIT and Harvard, Boston, Massachusetts, USA. [4] Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
23
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA. [4].
24
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Boston, Massachusetts, USA. [3] Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA. [4].
25
1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA. [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA. [4] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [5].

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.

PMID:
24413733
PMCID:
PMC3982316
DOI:
10.1038/ng.2868
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center