Universität zu Köln

Plum, Patrick Sven, Loeser, Heike, Zander, Thomas, Essakly, Ahlem, Bruns, Christiane J., Hillmer, Axel M., Alakus, Hakan, Schroeder, Wolfgang, Buttner, Reinhard, Gebauer, Florian and Quaas, Alexander . GATA binding protein 6 (GATA6) is co-amplified with PIK3CA in patients with esophageal adenocarcinoma and is linked to neoadjuvant therapy. J. Cancer Res. Clin. Oncol.. NEW YORK: SPRINGER. ISSN 1432-1335

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Abstract

Purpose Driver mutations are typically absent in esophageal adenocarcinoma (EAC). Mostly, oncogenes are amplified as driving molecular events (including GATA6-amplification in 14% of cases). However, only little is known about its biological function and clinical relevance. Methods We examined a large number of EAC (n = 496) for their GATA6 amplification by fluorescence in situ hybridization (FISH) analyzing both primary resected (n = 219) and neoadjuvant treated EAC (n = 277). Results were correlated to clinicopathological data and known mutations/amplifications in our EAC-cohort. Results GATA6 amplification was detectable in 49 (9.9%) EACs of our cohort. We observed an enrichment of GATA6-positive tumors among patients after neoadjuvant treatment (12,3% amplified tumors versus 6,8% in the primary resected group; p = 0.044). Additionally, there was a simultaneous amplification of PIK3CA and GATA6 (p < 0.001) not detectable when analyzing other genes such as EGFR, ERBB2, KRAS or MDM2. Although we did not identify a survival difference depending on GATA6 in the entire cohort (p = 0.212), GATA6 amplification was associated with prolonged overall survival among patients with primary surgery (median overall-survival 121.1 vs. 41.4 months, p = 0.032). Multivariate cox-regression analysis did not confirm GATA6 as an independent prognostic marker, neither in the entire cohort (p = 0.210), nor in the subgroup with (p = 0.655) or without pretreatment (p = 0.961). Conclusions Our study investigates the relevance of GATA6 amplification on a large tumor collective, which includes primary resected tumors and the clinically relevant group of neoadjuvant treated EACs. Especially in the pretreated group, we found an accumulation of GATA6-amplified tumors (12.3%) and a frequent co-amplification of PIK3CA. Our data suggest an increased resistance to radio-chemotherapy in GATA6-amplified tumors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Plum, Patrick Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeser, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Essakly, Ahlem UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmer, Axel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Buttner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-308367
DOI:	10.1007/s00432-020-03486-2
Journal or Publication Title:	J. Cancer Res. Clin. Oncol.
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1335
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language JUNCTIONAL CANCER; POOR-PROGNOSIS; EXPRESSION; METASTASIS; CHEMORADIOTHERAPY; MIGRATION; PROMOTES Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30836