PMID- 28529740
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2049-9450 (Print)
IS  - 2049-9469 (Electronic)
IS  - 2049-9450 (Linking)
VI  - 6
IP  - 5
DP  - 2017 May
TI  - Copy-number variation and protein expression of DOT1L in pancreatic 
      adenocarcinoma as a potential drug target.
PG  - 639-642
LID - 10.3892/mco.2017.1194 [doi]
AB  - Adenocarcinoma of the pancreas has a poor prognosis. At present, no relevant 
      personalized targets have been identified. Sequencing studies have implicated 
      gene alterations of disruptor of telomeric silencing 1 like histone lysine 
      methyltransferase (DOT1L) in pancreatic adenocarcinoma. DOT1L is part of the 
      histone modification system and catalyzes methylation of H3K79, which is crucial 
      in cell signaling and DNA damage repair. DOT1L is considered to be a target of 
      therapy in mixed lineage leukemia gene-deficient leukemia cases and a potential 
      target in breast carcinoma. The frequencies and importance of DOT1L copy-number 
      variations and their specific correlation with protein expression in 
      adenocarcinoma of the pancreas have yet to be investigated. In the present study, 
      tissue microarrays of 230 resected pancreatic adenocarcinoma cases were 
      constructed. The tumor tissue was analyzed using fluorescence in situ 
      hybridization (FISH) and immunohistochemistry. In total, 10/225 carcinoma cases 
      (4.4%) analyzed by immunohistochemistry demonstrated intense nuclear protein 
      expression of DOT1L and in 9/224 tumors analyzed using FISH (4.0%), copy-number 
      variations (CNV) were detectable. No DOT1L amplification was detected in the 
      carcinoma cohort. To the best of our knowledge, the present study describes for 
      the first time the frequency of CNV of DOT1L using the gold standard fluorescence 
      in situ hybridization (FISH) and their specific correlation to the protein 
      expression in adenocarcinomas of the pancreas. Although the positive cases by 
      immunohistochemistry and copy-number variations by FISH were not congruent with 
      each other, the data suggest a potential role for DOT1L in a small subset of 
      pancreatic cancer cases. The significance of the two analysis methods concerning 
      their druggability in pancreatic adenocarcinoma requires further studies.
FAU - Loeser, Heike
AU  - Loeser H
AD  - Institute of Pathology, University of Cologne, Gastrointestinal Cancer Group 
      Cologne, D-50937 Cologne, Germany.
FAU - Waldschmidt, Dirk
AU  - Waldschmidt D
AD  - Department of Gastroenterology and Hepatology, University of Cologne, 
      Gastrointestinal Cancer Group Cologne, D-50937 Cologne, Germany.
FAU - Kuetting, Fabian
AU  - Kuetting F
AD  - Department of Gastroenterology and Hepatology, University of Cologne, 
      Gastrointestinal Cancer Group Cologne, D-50937 Cologne, Germany.
FAU - Heydt, Carina
AU  - Heydt C
AD  - Institute of Pathology, University of Cologne, Gastrointestinal Cancer Group 
      Cologne, D-50937 Cologne, Germany.
FAU - Zander, Thomas
AU  - Zander T
AD  - Department of Oncology and Hematology, University of Cologne, Gastrointestinal 
      Cancer Group Cologne, D-50937 Cologne, Germany.
FAU - Plum, Patrick
AU  - Plum P
AD  - Department of Visceral Surgery, University of Cologne, Gastrointestinal Cancer 
      Group Cologne, D-50937 Cologne, Germany.
FAU - Alakus, Hakan
AU  - Alakus H
AD  - Department of Visceral Surgery, University of Cologne, Gastrointestinal Cancer 
      Group Cologne, D-50937 Cologne, Germany.
FAU - Buettner, Reinhard
AU  - Buettner R
AD  - Institute of Pathology, University of Cologne, Gastrointestinal Cancer Group 
      Cologne, D-50937 Cologne, Germany.
FAU - Quaas, Alexander
AU  - Quaas A
AD  - Institute of Pathology, University of Cologne, Gastrointestinal Cancer Group 
      Cologne, D-50937 Cologne, Germany.
LA  - eng
PT  - Journal Article
DEP - 20170314
PL  - England
TA  - Mol Clin Oncol
JT  - Molecular and clinical oncology
JID - 101613422
PMC - PMC5432215
OTO - NOTNLM
OT  - DOT1L
OT  - copy-number variations
OT  - fluorescence in situ hybridization
OT  - immunohistochemistry
OT  - pancreatic adenocarcinoma
OT  - personalized therapy
EDAT- 2017/05/23 06:00
MHDA- 2017/05/23 06:01
PMCR- 2017/03/14
CRDT- 2017/05/23 06:00
PHST- 2016/10/05 00:00 [received]
PHST- 2017/02/14 00:00 [accepted]
PHST- 2017/05/23 06:00 [entrez]
PHST- 2017/05/23 06:00 [pubmed]
PHST- 2017/05/23 06:01 [medline]
PHST- 2017/03/14 00:00 [pmc-release]
AID - MCO-0-0-1194 [pii]
AID - 10.3892/mco.2017.1194 [doi]
PST - ppublish
SO  - Mol Clin Oncol. 2017 May;6(5):639-642. doi: 10.3892/mco.2017.1194. Epub 2017 Mar 
      14.