Journal Article

DKFZ-2019-02462

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Germline GPR161 Mutations Predispose to Pediatric Medulloblastoma.

Begemann, M. ; Waszak, S. M. ; Robinson, G. W. ; Jäger, N.DKFZ* ; Sharma, T.DKFZ* ; Knopp, C. ; Kraft, F. ; Moser, O. ; Mynarek, M. ; Guerrini-Rousseau, L. ; Brugieres, L. ; Varlet, P. ; Pietsch, T. ; Bowers, D. C. ; Chintagumpala, M. ; Sahm, F.DKFZ* ; Korbel, J. O. ; Rutkowski, S. ; Eggermann, T. ; Gajjar, A. ; Northcott, P. ; Elbracht, M. ; Pfister, S. M.DKFZ* ; Kontny, U. ; Kurth, I.

2020
American Society of Clinical Oncology Alexandria, Va.

This record in other databases:  

Please use a persistent id in citations: doi:10.1200/JCO.19.00577

Abstract: The identification of a heritable tumor predisposition often leads to changes in management and increased surveillance of individuals who are at risk; however, for many rare entities, our knowledge of heritable predisposition is incomplete.Families with childhood medulloblastoma, one of the most prevalent childhood malignant brain tumors, were investigated to identify predisposing germline mutations. Initial findings were extended to genomes and epigenomes of 1,044 medulloblastoma cases from international multicenter cohorts, including retrospective and prospective clinical studies and patient series.We identified heterozygous germline mutations in the G protein-coupled receptor 161 (GPR161) gene in six patients with infant-onset medulloblastoma (median age, 1.5 years). GPR161 mutations were exclusively associated with the sonic hedgehog medulloblastoma (MBSHH) subgroup and accounted for 5% of infant MBSHH cases in our cohorts. Molecular tumor profiling revealed a loss of heterozygosity at GPR161 in all affected MBSHH tumors, atypical somatic copy number landscapes, and no additional somatic driver events. Analysis of 226 MBSHH tumors revealed somatic copy-neutral loss of heterozygosity of chromosome 1q as the hallmark characteristic of GPR161 deficiency and the primary mechanism for biallelic inactivation of GPR161 in affected MBSHH tumors.Here, we describe a novel brain tumor predisposition syndrome that is caused by germline GPR161 mutations and characterized by MBSHH in infants. Additional studies are needed to identify a potential broader tumor spectrum associated with germline GPR161 mutations.

Note: 2020 Jan 1;38(1):43-50.

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)
2. KKE Neuropathologie (B300)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 25 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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