High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting

Cancer Biol Ther. 2022 Dec 31;23(1):1-6. doi: 10.1080/15384047.2022.2128608.

Abstract

Next-generation sequencing data is fundamentally changing the clinical management of patients with cancer. The most frequent genomic alterations in malignancy are mutations and amplifications, with a subset of tumors having multiple amplifications - "amplificators". We sought to understand the molecular correlates of high tumor amplification burden in a pan-cancer context. Using both national registries and a single-institution dataset, our results demonstrate that cancers with TP53 mutations (as compared to those with wild-type TP53) exhibited significantly higher tumor amplification burden across all datasets. Amplifications, generally associated with overexpression, may be potentially actionable secondary consequences of TP53 mutations.

Keywords: TP53; amplifications; cancer genes; next-generation sequencing.

MeSH terms

  • Biomarkers, Tumor / genetics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Mutation
  • Neoplasms* / genetics
  • Tumor Burden
  • Tumor Suppressor Protein p53* / genetics

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53