Charmpi, Konstantina, Guo, Tiannan, Zhong, Qing, Wagner, Ulrich, Sun, Rui, Toussaint, Nora C., Fritz, Christine E., Yuan, Chunhui, Chen, Hao, Rupp, Niels J., Christiansen, Ailsa, Rutishauser, Dorothea, Ruschoff, Jan H., Fankhauser, Christian, Saba, Karim, Poyet, Cedric, Hermanns, Thomas, Oehl, Kathrin, Moore, Ariane L., Beisel, Christian, Calzone, Laurence, Martignetti, Loredana, Zhang, Qiushi, Zhu, Yi, Martinez, Maria Rodriguez, Manica, Matteo, Haffner, Michael C., Aebersold, Ruedi, Wild, Peter J. and Beyer, Andreas (2020). Convergent network effects along the axis of gene expression during prostate cancer progression. Genome Biol., 21 (1). LONDON: BMC. ISSN 1474-760X

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Abstract

Background Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels and consequently biochemical states of tumor tissues. Results Here, we investigate the propagation of genomic effects along the axis of gene expression during prostate cancer progression. We quantify genomic, transcriptomic, and proteomic alterations based on 105 prostate samples, consisting of benign prostatic hyperplasia regions and malignant tumors, from 39 prostate cancer patients. Our analysis reveals the convergent effects of distinct copy number alterations impacting on common downstream proteins, which are important for establishing the tumor phenotype. We devise a network-based approach that integrates perturbations across different molecular layers, which identifies a sub-network consisting of nine genes whose joint activity positively correlates with increasingly aggressive tumor phenotypes and is predictive of recurrence-free survival. Further, our data reveal a wide spectrum of intra-patient network effects, ranging from similar to very distinct alterations on different molecular layers. Conclusions This study uncovers molecular networks with considerable convergent alterations across tumor sites and patients. It also exposes a diversity of network effects: we could not identify a single sub-network that is perturbed in all high-grade tumor regions.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Charmpi, KonstantinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guo, TiannanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhong, QingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, RuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toussaint, Nora C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritz, Christine E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yuan, ChunhuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, HaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rupp, Niels J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christiansen, AilsaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rutishauser, DorotheaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruschoff, Jan H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fankhauser, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saba, KarimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poyet, CedricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermanns, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oehl, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, Ariane L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beisel, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Calzone, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martignetti, LoredanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, QiushiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, YiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez, Maria RodriguezUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manica, MatteoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haffner, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aebersold, RuediUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wild, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-308173
DOI: 10.1186/s13059-020-02188-9
Journal or Publication Title: Genome Biol.
Volume: 21
Number: 1
Date: 2020
Publisher: BMC
Place of Publication: LONDON
ISSN: 1474-760X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HISTONE METHYLTRANSFERASE SETDB1; ISUP CONSENSUS-CONFERENCE; MESSENGER-RNA; MASS-SPECTROMETRY; DRUG-RESISTANCE; PROTEIN; LANDSCAPE; STABILITY; REPAIR; GENOMEMultiple languages
Biotechnology & Applied Microbiology; Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/30817

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