TSGene 2.0: an updated literature-based knowledgebase for tumor suppressor genes

Abstract

Tumor suppressor genes (TSGs) are a major type of gatekeeper genes in the cell growth. A knowledgebase with the systematic collection and curation of TSGs in multiple cancer types is critically important for further studying their biological functions as well as for developing therapeutic strategies. Since its development in 2012, the Tumor Suppressor Gene database (TSGene), has become a popular resource in the cancer research community. Here, we reported the TSGene version 2.0, which has substantial updates of contents (e.g. up-to-date literature and pan-cancer genomic data collection and curation), data types (noncoding RNAs and protein-coding genes) and content accessibility. Specifically, the current TSGene 2.0 contains 1217 human TSGs (1018 protein-coding and 199 non-coding genes) curated from over 9000 articles. Additionally, TSGene 2.0 provides thousands of expression and mutation patterns derived from pan-cancer data of The Cancer Genome Atlas. A new web interface is available at http://bioinfo.mc.vanderbilt.edu/TSGene/. Systematic analyses of 199 non-coding TSGs provide numerous cancer-specific non-coding mutational events for further screening and clinical use. Intriguingly, we identified 49 protein-coding TSGs that were consistently down-regulated in 11 cancer types. In summary, TSGene 2.0, which is the only available database for TSGs, provides the most updated TSGs and their features in pan-cancer.

Figure 1.

Alteration landscape of the 19 long noncoding RNA (lncRNA) TSGs in pan-cancer. (A) Alteration profiles of 19 lncRNA TSGs in 25 major cancer types with alteration frequency ≥10% in each cancer type. (B) Sample-based distribution of alterations in 19 lncRNA TSGs in TCGA prostate cancer data. CNA: copy number alteration. Multiple alterations: more than one type of mutations. All the mutational analyses were conducted based on the cBIO portal data (45).

Figure 2.

Mutational landscape of the 24 top-ranked microRNA (miRNA) TSGs in pan-cancer. (A) Somatic mutational patterns of 24 top-ranked miRNA TSGs in multiple cancer types. (B) Sample-based copy number alteration covering 9 miRNA TSGs in TCGA high-grade glioblastoma. (C) Global somatic mutations of has-miR-31 in multiple cancer types. All the mutational analyses were conducted based on the cBIO portal data (45).

Figure 3.

Biological features of 49 down-regulated TSGs in multiple cancer types. (A) Shared down-regulated TSGs in 11 major cancers. Eleven colors represent 11 cancer types, respectively. Lengths of the circularly arranged segments are proportional to the total number of TSGs in the 11 cancers. The three outer rings are stacked bar plots, representing relative overlap of other cancer TSGs to the cancer totals. Ribbons connecting different segments represent the number of shared TSGs between cancer types. (B) A microRNA regulatory network enriched with the 49 down-regulated TSGs. The network contains 16 microRNAs (red) and 45 down-regulated TSGs (blue) targeted by these connected microRNAs. (C) Global view of the somatic mutations in the 49 down-regulated TSGs in pan-cancer.