Universität zu Köln

Gruenewald, Inga, Trautmann, Marcel ORCID: 0000-0002-5842-1196, Busch, Alina, Bauer, Larissa, Huss, Sebastian, Schweinshaupt, Petra, Vollbrecht, Claudia, Odenthal, Margarete, Quaas, Alexander, Buettner, Reinhard, Meyer, Moritz F., Beutner, Dirk, Huettenbrink, Karl-Bernd, Wardelmann, Eva, Stenner, Markus and Hartmann, Wolfgang ORCID: 0000-0002-7609-5021 (2016). MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas. Oncotarget, 7 (46). S. 75261 - 75273. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are limited in SDC, while genomic rearrangements of the adjacent HMGA2 gene locus are well documented in subsets of SDCs. We here analyzed the mutational status of the TP53 gene, genomic amplification of MDM2, CDK4 and HMGA2 rearrangement/amplification as well as protein expression of TP53 (p53), MDM2 and CDK4 in 51 de novo and ex pleomorphic adenoma SDCs. 25 of 51 cases were found to carry TP53 mutations, associated with extreme positive immunohistochemical p53 staining levels in 13 cases. Three out of 51 tumors had an MDM2 amplification, one of them coinciding with a CDK4 amplification and two with a HMGA2 rearrangement/amplification. Two of the MDM2 amplifications occurred in the setting of a TP53 mutation. Two out of 51 cases showed a CDK4 amplification, one synchronously being MDM2 amplified and the other one displaying concurrent low copy number increases of both, MDM2 and HMGA2. In summary, we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. Further research is necessary to clarify the role of chromosomal region 12q13-15 alterations in SDC tumorigenesis and their potential prognostic and therapeutic relevance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gruenewald, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED Trautmann, Marcel UNSPECIFIED orcid.org/0000-0002-5842-1196 UNSPECIFIED Busch, Alina UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Larissa UNSPECIFIED UNSPECIFIED UNSPECIFIED Huss, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schweinshaupt, Petra UNSPECIFIED UNSPECIFIED UNSPECIFIED Vollbrecht, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Moritz F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beutner, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Huettenbrink, Karl-Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Wardelmann, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Stenner, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Wolfgang UNSPECIFIED orcid.org/0000-0002-7609-5021 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-255705
DOI:	10.18632/oncotarget.12127
Journal or Publication Title:	Oncotarget
Volume:	7
Number:	46
Page Range:	S. 75261 - 75273
Date:	2016
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-SITU HYBRIDIZATION; P53 PATHWAY; HMGI-C; OVEREXPRESSION; REARRANGEMENTS; ACTIVATION; REVEALS; GENE Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25570