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Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons80450

Mueller-Myhsok,  B.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Ruf, C. G., Schmelz, H.-U., Port, M., Wagner, W., Matthies, C., Mueller-Myhsok, B., et al. (2014). Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS. BRITISH JOURNAL OF CANCER, 110(11), 2738-2746. doi:10.1038/bjc.2014.134.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-CAEC-F
Abstract
Background: We aimed to better discriminate (occult) metastasised from non-metastasised seminoma based on transcriptional changes of small RNAs in the primary tumour. Methods: Total RNAs including small RNAs were isolated from five testicular tumours of each, lymphogenic, occult and non-metastasised patients. Next-generation sequencing (SOLID, Life Technologies) was used to examine transcriptional changes. Small RNAs showing <= X50 reads and a significant <= 2-fold difference using non-metastasised tumours as the reference group were examined in univariate logistic regression analysis and combinations of two small RNAs were further examined using support vector machines Results: On average, 1.3 x 10(7), 1.4 x 10(7) and 1.7 x 10(7) small RNA reads were detectable in non-metastasised, occult and lymphogenic metastasised seminoma, respectively, of which 30-32% remained after trimming. Between 59 and 68% represented annotated reads and between 8.6 and 11% were annotated small RNA tags. Of them, 137 small RNAs showed 450 reads and a two-fold difference to the reference. In univariate analysis, 32-38 small RNAs significantly discriminated lymphogenic/occult from non-metastasised seminoma, and among these different comparisons, it were the same small RNAs in 51-88%. Many combinations of two of these small RNAs allowed a complete discrimination of metastasised from non-metastasised seminoma irrespective of the metastasis subtype. Conclusions: Metastasised and non-metastasised seminoma can be completely discriminated with a combination of two small RNAs.