Universität zu Köln

Quaas, Alexander, Heydt, Carina, Gebauer, Florian, Alakus, Hakan, Loeser, Heike ORCID: 0000-0003-4555-1327, Buettner, Reinhard, Hillmer, Axel ORCID: 0000-0002-3381-7266, Bruns, Christiane, Merkelbach-Bruse, Sabine, Zander, Thomas and Frommolt, Peter ORCID: 0000-0002-1966-8014 (2019). Genomic Characterization of TP53-Wild-Type Esophageal Carcinoma. Transl. Oncol., 12 (1). S. 154 - 162. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1936-5233

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Abstract

Up to 40% of esophageal carcinomas have a biallelic intact TP53 gene. It is largely unclear how these carcinoma cells prevent apoptosis, what is the kind of pathway alterations, or whether therapeutically relevant alterations exist in this subgroup. We evaluated The Cancer Genome Atlas (TCGA) data to compare TP53-mutated with TP53 wild-type tumors regarding copy number variations, gene mutations, and expression patterns of protein-coding genes and miRNAs. Additionally, we analyzed up to 428 esophageal adenocarcinomas (EACs) in total using an ultra-deep parallel sequencing panel, immunohistochemistry, as well as fluorescence in situ hybridization. In the TCGA cohort, 17.3% has a biallelic intact TP53 gene. This group has a smaller average total size of somatic copy number variations. Some protein coding genes and miRNAs were differentially expressed between the TP53-wild-type and TP53-mutated group to emphasize mdm2, CCND2, TP73, or miRNA 150, 488, or 4662a. In addition, 50% of the TP53-wild-type tumors carry somatic mutations in at least one of the genes involved in the TP53 pathway. Our patient cohort revealed 41.3% TP53-wild-type tumors; 5.6% were MDM2 amplified. In accordance with the TCGA data, we did not find a prognostic relevance of TP53 in our tumor cohort as well. The mutation status of TP53 defines an important subtype in esophageal carcinoma. Our comprehensive molecular analysis revealed important and potentially therapeutically relevant genomic alterations in this subgroup.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeser, Heike UNSPECIFIED orcid.org/0000-0003-4555-1327 UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmer, Axel UNSPECIFIED orcid.org/0000-0002-3381-7266 UNSPECIFIED Bruns, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Frommolt, Peter UNSPECIFIED orcid.org/0000-0002-1966-8014 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-141000
DOI:	10.1016/j.tranon.2018.09.007
Journal or Publication Title:	Transl. Oncol.
Volume:	12
Number:	1
Page Range:	S. 154 - 162
Date:	2019
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1936-5233
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IDENTIFICATION; MICRORNA-34A; PROGRESSION; SENESCENCE; MUTATIONS; REGULATOR; PROTEIN; GENES; CELLS; P53 Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14100