Unveiling the signature of transposable elements-derived transcripts – the transposcriptome – as a biomarker in human acute myeloid leukemia

Project Information

LEUKEMIC-TEs

Grant agreement ID: 747203

DOI

10.3030/747203

Project closed

EC signature date 20 February 2017

Start date 1 April 2017

End date 31 March 2019

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 175 419,60

EU contribution

€ 175 419,60

Coordinated by

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland

Periodic Reporting for period 1 - LEUKEMIC-TEs (Unveiling the signature of transposable elements-derived transcripts – the transposcriptome – as a biomarker in human acute myeloid leukemia)

Reporting period: 2017-04-01 to 2019-03-31

Summary of the context and overall objectives of the project

The funding provided by the MSCA-IF together with the vast knowledge in transposable elements (TEs) of the host lab and the expertise of the applicant in the cancer field allowed us to perform an unprecedented characterisation of the expression of TEs in cancer. We focused on acute myeloid leukemia (work still in progress) and colorectal cancer, which promptly lead to the discovery of TE-based biomarkers (TEBBs) with high diagnostic, prognostic and theranostic value. The application of transposcriptomics (analysis of TE-derived transcripts) lead us to define biomarker-based signatures more performing than current methods for staging tumors, forecast their clinical course and predict their drug sensitivity. Accordingly, our results stand to have high impact on the clinical management of cancer patients.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We extracted patterns of TE expression from RNA-seq datasets of acute myeloid leukaemia (AML) and colorectal cancer (CRC) patients.
We developed an in-house bioinformatic pipeline aimed at discovering TE-driven transcripts that are fused to gene transcripts, yielding what we coined transpochimeric gene transcripts (TcGTs). We applied this analytical tool to AML, CRC and, later, to other cancer types.
We discovered TcGTs predictive of survival in CRC, including one encoding for what we demonstrated through both in vitro and in vivo experiments to be a so far unsuspected yet unequivocally oncogenic, metastasis-promoting factor.
We further established a catalogue of TEBBs correlating with the sensitivity and resistance of cancer cells to some 500 drugs. We are currently validating experimentally these predictions, as our results stand to influence profoundly cancer patients' therapeutic stratification.
Our results have been publicly disseminated through internal seminars, laboratory and institution retreats, international conferences and lectures to undergraduate students. One patent has already been filed with the help of the EPFL technology transfer office and a patent lawyer. A manuscript describing the CRC work is at an advanced stage of redaction. A second manuscript will focus on TEBBs that predict sensitivity or resistance to chemotherapy, after the corresponding approach and results will have been properly patented.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The host lab is pioneering the field of transposcriptomics, and my work demonstrates its enormous potential for cancer research and clinical management.
My result stand to influence cancer patients' clinical care by facilitating tumor staging, prognosis evaluation and personalized treatment. As such, my work is a significant contribution to precision oncology.
The launching of a start-up based on my results is in the works, as an indispensable step towards the clinical exploitation of my results.

TE_derived_information