Profiling of the metabolic transcriptome via single molecule molecular inversion probes

Tessa De Bitter, Carlijn Van De Water, Corina Van Den Heuvel, Carolien Zeelen, Astrid Eijkelenboom, Bastiaan Tops, Egbert Oosterwijk, Dimitar Kolev, Peter Mulders, Mark Ter Laan, Sanne Van Lith, William Leenders

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

10 Citaten (Scopus)

Samenvatting

Cancer-specific metabolic alterations are of high interest as therapeutic targets. These alterations vary between tumor types, and to employ metabolic targeting to its fullest potential there is a need for robust methods that identify candidate targetable metabolic pathways in individual cancers. Currently, such methods include 13C-tracing studies and mass spectrometry/ magnetic resonance spectroscopic imaging. Due to high cost and complexity, such studies are restricted to a research setting. We here present the validation of a novel technique of metabolic profiling, based on multiplex targeted next generation sequencing of RNA with single molecule molecular inversion probes (smMIPs), designed to measure activity of and mutations in genes that encode metabolic enzymes. We here profiled an isogenic pair of cell lines, differing in expression of the Von Hippel Lindau protein, an important regulator of hypoxia-inducible genes. We show that smMIP-profiling provides relevant information on active metabolic pathways. Because smMIP-based targeted RNAseq is cost-effective and can be applied in a medium high-throughput setting (200 samples can be profiled simultaneously in one next generation sequencing run) it is a highly interesting approach for profiling of the activity of genes of interest, including those regulating metabolism, in a routine patient care setting.

Originele taal-2Engels
Artikelnummer11402
TijdschriftScientific Reports
Volume7
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 1 dec. 2017
Extern gepubliceerdJa

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