INTRODUCTION: This study presents a novel molecular parameter potentially co-defining tumor biology-the total tumor suppressor gene (TSG) count at chromosomal loci harboring genes rearranged in fusion-defined tumors. It belongs to the family of molecular parameters created using a black-box approach. METHOD: It is based on a public curated Texas TSG database. Its data are regrouped based on individual genes loci using another public database (Genecards). The total TSG count for NTRK (NTRK1; OMIM: 191315; NTRK2; OMIM: 600456; NTRK3; OMIM: 191316), NRG1 (OMIM: 142445), and RET (OMIM: 164761) rearranged tumors in patients treated with a theranostic approach is calculated using the results of recently published studies. RESULTS: Altogether 138 loci containing at least three TSGs are identified. These include 21 "extremely hot" spots, with 10 to 28 TSGs mapping to a given locus. However, the study falls short of finding a correlation between tumor regression or patient survival and the TSG count owing to a low number of cases meeting the study criteria. CONCLUSION: The total TSG count alone cannot predict the biology of translocation-defined tumors. The addition of other parameters, including microsatellite instability (MSI), tumor mutation burden (TMB), homologous recombination repair deficiency (HRD), and copy number heterogeneity (CNH), might be helpful. Thus a multi-modal data integration is advocated. We believe that large scale studies should evaluate the significance and value of the total TSG count.

• Keywords
• artificial intelligence, cancer, chromosomal instability, chromothripsis, copy number heterogeneity, gene, gene rearrangement, homologous recombination repair, microsatellite instability, translocation, tumor mutation burden, tumor suppressor gene,
• MeSH
• Gene Fusion MeSH
• Genomics MeSH
• Humans MeSH
• Mutation MeSH
• Biomarkers, Tumor genetics   MeSH
• Neoplasms * genetics   pathology   MeSH
• Translocation, Genetic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers, Tumor MeSH