Universität zu Köln

Jansen, Ruben, Moehlendick, Birte, Bartenhagen, Christoph, Toth, Csaba, Lehwald, Nadja, Stoecklein, Nikolas H., Knoefel, Wolfram T. and Lachenmayer, Anja (2018). ACGH detects distinct genomic alterations of primary intrahepatic cholangiocarcinomas and matched lymph node metastases and identifies a poor prognosis subclass. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

Full text not available from this repository.

Abstract

Lymph node metastases (LNM) are an important prognostic factor for patients with intrahepatic cholangiocarcinoma, but underlying genetic alterations are poorly understood. Whole genome array comparative genomic hybridization (aCGH) was performed in 37 tumors and 14 matched LNM. Genomic analyses of tumors confirmed known and identified new (gains in 19q) copy number alterations (CNA). Tumors with LNM (N1) had more alterations and exclusive gains (3p, 4q, 5p, 13q) and losses (17p and 20p). LNM shared most alterations with their matched tumors (86%), but 79% acquired new isolated gains [12q14 (36%); 1p13, 2p23, 7p22, 7q11, 11q12, 13q13 and 14q12 (>20%)]. Unsupervised clustering revealed a poor prognosis subclass with increased alterations significantly associated to tumor differentiation and survival. TP53 and KRAS mutations occurred in 19% of tumors and 6% of metastases. Pathway analyses revealed association to cancer-associated pathways. Advanced tumor stage, microvascular/perineural invasion, and microscopic positive resection margin (R1) were significantly correlated to metastases, while N1-status, R1-resection, and poor tumor differentiation were significantly correlated to survival. ACGH identified clear differences between N0 (no LNM) and N1 tumors, while N1 tumors and matched LNM displayed high clonality with exclusive gains in the metastases. A novel subclass with increased CNAs and poor tumor differentiation was significantly correlated to survival.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jansen, Ruben UNSPECIFIED UNSPECIFIED UNSPECIFIED Moehlendick, Birte UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartenhagen, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Toth, Csaba UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehwald, Nadja UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoecklein, Nikolas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knoefel, Wolfram T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lachenmayer, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-179743
DOI:	10.1038/s41598-018-28941-6
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN HILAR CHOLANGIOCARCINOMA; SQUAMOUS-CELL CARCINOMA; BILIARY-TRACT CANCERS; COPY NUMBER CHANGES; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; EXPRESSION PATTERNS; BREAST-CANCER; HYBRIDIZATION; PROGRESSION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17974