Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations

EMBO Mol Med. 2017 Apr;9(4):498-507. doi: 10.15252/emmm.201606660.


Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53-intact tumors (P ≪ 10-10), and shRNA-mediated knockdown of RPGs activated p53 in TP53-wild-type cells. In contrast, we did not see negative selection of RPG deletions in TP53-mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically.

Keywords: cancer; ribosomal gene haploinsufficiency; ribosome function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation*
  • Neoplasms / pathology*
  • Ribosomal Proteins / genetics*
  • Tumor Suppressor Protein p53 / genetics*


  • Ribosomal Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53