Gruenewald, Inga, Vollbrecht, Claudia ORCID: 0000-0002-0861-001X, Meinrath, Jeannine, Meyer, Moritz F., Heukamp, Lukas C., Drebber, Uta, Quaas, Alexander, Beutner, Dirk, Huettenbrink, Karl-Bernd, Wardelmann, Eva, Hartmann, Wolfgang ORCID: 0000-0002-7609-5021, Buettner, Reinhard, Odenthal, Margarete and Stenner, Markus (2015). Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity. Oncotarget, 6 (20). S. 18224 - 18238. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Salivary gland cancer represents a heterogeneous group of malignant tumors. Due to their low incidence and the existence of multiple morphologically defined subtypes, these tumors are still poorly understood with regard to their molecular pathogenesis and therapeutically relevant genetic alterations. Performing a systematic and comprehensive study covering 13 subtypes of salivary gland cancer, next generation sequencing was done on 84 tissue samples of parotid gland cancer using multiplex PCR for enrichment of cancer related gene loci covering hotspots of 46 cancer genes. Mutations were identified in 22 different genes. The most frequent alterations affected TP53, followed by RAS genes, PIK3CA, SMAD4 and members of the ERB family. HRAS mutations accounted for more than 90% of RAS mutations, occurring especially in epithelial-myoepithelial carcinomas and salivary duct carcinomas. Additional mutations in PIK3CA also affected particularly epithelial-myoepithelial carcinomas and salivary duct carcinomas, occurring simultaneously with HRAS mutations in almost all cases, pointing to an unknown and therapeutically relevant molecular constellation. Interestingly, 14% of tumors revealed mutations in surface growth factor receptor genes including ALK, HER2, ERBB4, FGFR, cMET and RET, which might prove to be targetable by new therapeutic agents. 6% of tumors revealed mutations in SMAD4. In summary, our data provide novel insight into the fundamental molecular heterogeneity of salivary gland cancer, relevant in terms of tumor classification and the establishment of targeted therapeutic concepts.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gruenewald, IngaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vollbrecht, ClaudiaUNSPECIFIEDorcid.org/0000-0002-0861-001XUNSPECIFIED
Meinrath, JeannineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, Moritz F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drebber, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beutner, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huettenbrink, Karl-BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wardelmann, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, WolfgangUNSPECIFIEDorcid.org/0000-0002-7609-5021UNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stenner, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-398712
Journal or Publication Title: Oncotarget
Volume: 6
Number: 20
Page Range: S. 18224 - 18238
Date: 2015
Publisher: IMPACT JOURNALS LLC
Place of Publication: ORCHARD PARK
ISSN: 1949-2553
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SALIVARY DUCT CARCINOMA; CELL LUNG-CANCER; ADENOID CYSTIC CARCINOMA; ADVANCED COLORECTAL-CANCER; IN-SITU HYBRIDIZATION; KINASE INHIBITORS; MUTATIONAL STATUS; RAS MUTATIONS; PATHWAY; RESISTANCEMultiple languages
Oncology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39871

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