Copy-number variation and protein expression of DOT1L in pancreatic adenocarcinoma as a potential drug target

Molecular and Clinical Oncology
Heike LoeserAlexander Quaas

Abstract

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 coh...Continue Reading

References

Jul 5, 2002·The Journal of Biological Chemistry·Nicolas LacosteJacques Côte
Apr 27, 2005·Cell·Yuki OkadaYi Zhang
Sep 4, 2010·Nature Reviews. Cancer·John P MorrisMatthias Hebrok
Jun 27, 2013·Blood·Scott R DaigleRoy M Pollock
May 27, 2014·PloS One·Wei LiuMichele Redell
Jan 31, 2015·Current Opinion in Hematology·Eytan M Stein, Martin S Tallman
Aug 6, 2015·Postgraduate Medical Journal·Tamara M H GallLong R Jiao
Oct 2, 2015·Oncotarget·Jeong-Yeon Lee, Gu Kong
Dec 25, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Kyoichi TakaoriUNKNOWN IAP/EPC study group on the clinical managements of pancreatic cancer
May 7, 2016·Current Opinion in Genetics & Development·Xi WangScott A Armstrong
May 29, 2016·Mutation Research. Reviews in Mutation Research·Zeenat FarooqMohammad Altaf
Sep 10, 2016·World Journal of Gastroenterology : WJG·Chiara CaparelloElisa Giovannetti

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Methods Mentioned

BETA
light microscopy

Clinical Trials Mentioned

NCT01684150

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