Genome-wide iRNA screening identifies novel aneuploidy inducing gene knockdowns that transform telomerase positive human cells

6^th International Conference on Genomics & Pharmacogenomics

September 12-14, 2016 Berlin, Germany

Cagatay Gunes, Jitendra K Meena, Johann M Kraus, Sarah-Fee Katz, Andre Lechel, Hans A Kestler and Karl L Rudolph

Leibniz Institute of Age Research-Fritz Lipmann Institute e.V., Germany
Ulm University, Germany

Posters & Accepted Abstracts: J Mol Genet Med

Abstract :

Aneuploidy represents a hallmark feature of aging associated carcinogenesis in humans but mutations in the classical ploidy control genes are rare in human tumors as these mutations reduce cell fitness. Recent data indicate that aneuploidy can inhibit or instigate tumorigenesis dependent on the genetic background. These observations imply that aneuploidy induction involves mechanisms that allow survival of aneuploid cells. Here, genome-wide, stable iRNA screening identified a large set of gene knockdowns with a novel role in aneuploidy induction in human cells. These gene knockdowns strongly associate with recurrent gene mutations in human cancer. Anchorage-independent growth and xenotransplantation experiments indicate that aneuploidy inducing gene knockdowns replace the requirement of iatrogenic introduction of oncogenic Ras for the malignant transformation of telomerase-positive primary human cells. Together, this study identifies cancer associated gene deletions that induce aneuploidy and malignant transformation of human cells in the presence of telomerase.

Biography :

Email: cagatay.guenes@leibniz-fli.de cagatay.guenes@uniklinik-ulm.de