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TP53 isoform junction reads based analysis in malignant and normal contexts

Suleyman Vural1,2, Lun-Ching Chang3, Laura M Yee1

  • 1National Cancer Institute, Division of Cancer Treatment and Diagnosis, Biometric Research Program, Rockville, MD, 20850, USA.

Scientific Reports
|August 27, 2021
PubMed

Insights

The TP53 gene

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The TP53 gene is frequently altered in cancer, with NM_000546.6 being the predominant isoform.
  • Alternative TP53 isoforms exist at lower expression levels and may have altered tumor suppressor activity.

Purpose of the Study:

  • To investigate the expression patterns of TP53 alternative isoforms in cancer and normal tissues.
  • To determine if TP53 C-terminal alternative isoforms increase in tumors with wild-type TP53.

Main Methods:

  • Analysis of exon-exon junction reads from RNA-seq data.
  • Utilized datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) projects.

Main Results:

  • Observed no substantial increase in the fraction of TP53 C-terminal alternative isoforms in TCGA tumors and CCLE cell lines with wild-type TP53.
  • Contrary to expectations, TP53 C-terminal alternative isoforms did not significantly increase in tumors with wild-type TP53.

Conclusions:

  • TP53 C-terminal alternative isoforms, which have reduced tumor suppressor activity, are not significantly selected for during tumor progression.
  • The expression of TP53 alternative isoforms may not be a reliable indicator for tumor progression in wild-type TP53 cancers.

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