Universität zu Köln

Loeser, Heike ORCID: 0000-0003-4555-1327, Woelwer, Christina B., Alakus, Hakan ORCID: 0000-0002-3889-3276, Chon, Seung-Hun ORCID: 0000-0002-8923-6428, Zander, Thomas, Buettner, Reinhard, Hillmer, Axel M., Bruns, Christiane J., Schroeder, Wolfgang, Gebauer, Florian ORCID: 0000-0001-5312-4814 and Quaas, Alexander (2020). Y Chromosome Loss Is a Frequent Event in Barrett's Adenocarcinoma and Associated with Poor Outcome. Cancers, 12 (7). BASEL: MDPI. ISSN 2072-6694

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Abstract

Background: The loss of the Y chromosome in various malignant diseases has been described previously. There are no reliable information on the actual frequency, significance and homogeneity of Y chromosome loss (LoY) in esophageal adenocarcinoma (EAC). Methods: 400 male EAC including lymph-node metastases were analyzed with commercially available Y chromosome specific fluorescence in-situ probes. The results were correlated with molecular and immunohistochemical markers and clinicopathological aspects. Results: The entire cohort (n= 400) showed a singularLoYof one chromosome arm in 1.0% (q-arm) and 2.8% (p-arm), completeLoYin 52.5%.LoYwas strongly associated with shortened overall-survival (OS). Patients with preserved Y chromosome had a median OS of 58.8 months, patients withLoYan OS of 19.4 months (p< 0.001). Multivariate analysis showedLoYas an independent prognostic marker with a hazard ratio of 1.835 (95% CI 1.233-2.725).LoYcorrelated withTP53mutations (p= 0.003),KRASamplification (p= 0.004), loss of ARID1a (p= 0.045) and presence of LAG3 (p= 0.018). Conclusions: Loss of the Y chromosome is a very common phenomenon in EAC. TheLoYis heterogeneously distributed within the tumor, but corresponding lymph node metastases frequently show homogeneousLoY,indicating a selection and metastasizing advantage with poor prognosis. To date, the male predominance of EAC (7-9:1) is unclear, so genetic explanatory models are favored. TheLoYin EAC may be biologically and functionally relevant and additional genomic or functional analyses are needed.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Loeser, Heike UNSPECIFIED orcid.org/0000-0003-4555-1327 UNSPECIFIED Woelwer, Christina B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED orcid.org/0000-0002-3889-3276 UNSPECIFIED Chon, Seung-Hun UNSPECIFIED orcid.org/0000-0002-8923-6428 UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmer, Axel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Florian UNSPECIFIED orcid.org/0000-0001-5312-4814 UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-327452
DOI:	10.3390/cancers12071743
Journal or Publication Title:	Cancers
Volume:	12
Number:	7
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANDIDATE TUMOR-SUPPRESSOR; ESOPHAGEAL ADENOCARCINOMA; BLOOD-CELLS; MOSAIC LOSS; DISEASE; CANCER; RISK; MECHANISMS; KDM5D Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32745