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| Status |
Public on Jul 09, 2016 |
| Title |
Aberrant downstream mechanisms following loss of KMT2C and KMT2D in Pancreatic Ductal Adenocarcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Genes encoding the histone H3 lysine 4 (H3K4) methyltransferases KMT2C and KMT2D are subject to deletion and mutation in pancreatic ductal adenocarcinomas (PDAC). We examined the functional and transcriptional consequences of loss of these methyltransferases in patients with PDAC. Patients with low KMT2C and KMT2D expression demonstrated a much-improved outcome compared with those expressing high levels. RNA-seq analysis of KMT2C or KMT2D loss in three cell lines (PANC1, SUIT2 and COLO357) identified 31 and 124 differentially expressed genes respectively, with 19 genes common to both methlytransferases. Gene set enrichment analysis, and correlation with publicly available patient gene expression (GEP) datasets, highlighted significant reductions in pathways relating to cell-cycle and cell growth, where gene expression correlated with KMT2C/D depletion. Furthermore, loss of Kmt2d in three murine cell lines increased sensitivity to the nucleoside analogue 5-fluorouracil (5FU). These experiments support critical, non-redundant, roles for KMT2D and KMT2C in PDAC, where depletion impacts cell-cycle to reduce cell proliferation, enhance response to specific chemotherapy, which may improve patient survival.
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| Overall design |
Investigation of changes in whole transcriptomes with KMT2C/D loss by siRNAs using RNA-seq in three human cell lines
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| Contributor(s) |
Dawkins J, Wang J, Fitzgibbon J, Grose R |
| Citation(s) |
27280393 |
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| Submission date |
Nov 24, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jun Wang |
| E-mail(s) |
j.a.wang@qmul.ac.uk
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| Organization name |
Barts Cancer Institute, Queen Mary, London
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| Street address |
Charterhouse Square
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| City |
London |
| ZIP/Postal code |
EC1M 6BQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA304108 |
| SRA |
SRP066663 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE75327_RAW.tar |
3.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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