Universität zu Köln

Gultekin, Sibel Elif, Aziz, Reem, Heydt, Carina, Senguven, Burcu, Zoller, Joachim, Safi, Ali Farid, Kreppel, Matthias and Buettner, Reinhard (2018). The landscape of genetic alterations in ameloblastomas relates to clinical features. Virchows Arch., 472 (5). S. 807 - 815. NEW YORK: SPRINGER. ISSN 1432-2307

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Abstract

Ameloblastoma is a mostly benign, but locally invasive odontogenic tumor eliciting frequent relapses and significant morbidity. Recently, mutually exclusive mutations in BRAF and SMO were identified causing constitutive activation of MAPK and hedgehog signaling pathways. To explore further such clinically relevant genotype-phenotype correlations, we here comprehensively analyzed a large series of ameloblastomas (98 paraffin block of 76 patients) with respect to genomic alterations, clinical presentation, and histological features collected from the archives of three different pathology centers in France, Germany, and Turkey. In good agreement with previously published data, we observed BRAF mutations almost exclusively in mandibular tumors, SMO mutations predominantly in maxillary tumors, and single mutations in EGFR, KRAS, and NRAS. KRAS, NRAS, PIK3CA, PTEN, CDKN2A, FGFR, and CTNNB1 mutations co-occurred in the background of either BRAF or SMO mutations. Strikingly, multiple mutations were exclusively observed in European patients, in solid ameloblastomas and were associated with a very high risk for recurrence. In contrast, tumors with a single BRAF mutation revealed a lower risk for relapse. We here establish a comprehensive landscape of mutations in the MAPK and hedgehog signaling pathways relating to clinical features of ameloblastoma. Our data suggest that ameloblastomas harboring single BRAF mutations are excellent candidates for neo-adjuvant therapies with combined BRAF/MEK inhibitors and that the risk of recurrence maybe stratified based on the mutational spectrum.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gultekin, Sibel Elif UNSPECIFIED UNSPECIFIED UNSPECIFIED Aziz, Reem UNSPECIFIED UNSPECIFIED UNSPECIFIED Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Senguven, Burcu UNSPECIFIED UNSPECIFIED UNSPECIFIED Zoller, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Safi, Ali Farid UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreppel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-187679
DOI:	10.1007/s00428-018-2305-5
Journal or Publication Title:	Virchows Arch.
Volume:	472
Number:	5
Page Range:	S. 807 - 815
Date:	2018
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-2307
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUTATIONS; PATHWAY Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18767