Oncotarget

Research Papers:

The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types

Laura Fancello, Kim R. Kampen, Isabel J.F. Hofman, Jelle Verbeeck and Kim De Keersmaecker _

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Oncotarget. 2017; 8:14462-14478. https://doi.org/10.18632/oncotarget.14895

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Abstract

Laura Fancello1,*, Kim R. Kampen1,*, Isabel J.F. Hofman1, Jelle Verbeeck1 and Kim De Keersmaecker1

1 KU Leuven-University of Leuven, Department of Oncology, LKI-Leuven Cancer Institute, Leuven, Belgium

* These authors have contributed equally to this work

Correspondence to:

Kim De Keersmaecker, email:

Keywords: ribosomal protein, haploinsufficient tumor suppressor, TCGA, breast cancer

Received: January 05, 2017 Accepted: January 11, 2017 Published: January 29, 2017

Abstract

For many years, defects in the ribosome have been associated to cancer. Recently, somatic mutations and deletions affecting ribosomal protein genes were identified in a few leukemias and solid tumor types. However, systematic analysis of all 81 known ribosomal protein genes across cancer types is lacking. We screened mutation and copy number data of respectively 4926 and 7322 samples from 16 cancer types and identified six altered genes (RPL5, RPL11, RPL23A, RPS5, RPS20 and RPSA). RPL5 was located at a significant peak of heterozygous deletion or mutated in 11% of glioblastoma, 28% of melanoma and 34% of breast cancer samples. Moreover, patients with low RPL5 expression displayed worse overall survival in glioblastoma and in one breast cancer cohort. RPL5 knockdown in breast cancer cell lines enhanced G2/M cell cycle progression and accelerated tumor progression in a xenograft mouse model. Interestingly, our data suggest that the tumor suppressor role of RPL5 is not only mediated by its known function as TP53 or c-MYC regulator. In conclusion, RPL5 heterozygous inactivation occurs at high incidence (11-34%) in multiple tumor types, currently representing the most common somatic ribosomal protein defect in cancer, and we demonstrate a tumor suppressor role for RPL5 in breast cancer.


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