Scholarlink

<p>Polymerase theta <i>(POLθ)</i> inhibitors were developed to overcome resistance to PARP inhibitor treatment in homologous recombination (HR) deficient cancer. Biomarkers identifying PARP inhibitor-resistant cancer cases that specifically rely on <i>POLθ</i> activity for cancer cell survival will help to identify the sensitive patient population. From the TCGA RNAseq data, we determined <i>POLθ</i> expression levels, and from whole-exome and whole-genome sequencing data, we determined the number of <i>POLθ</i>-associated mutational signatures in solid tumors with various HR deficiency status. We found that <i>POLθ</i> expression levels did not differ significantly between HR-proficient and HR-deficient cancers. However, <i>POLθ</i> expression correlated strongly with proliferation-associated gene expression signatures and was predominantly observed in the S and G2/M phases of the cell cycle. <i>POLθ</i>-associated mutational signatures are correlated with <i>POLθ</i> expression levels only in BRCA2-deficient cancers. <i>POLθ</i> expression level and <i>POLθ</i>-associated mutational signatures may be indicative of <i>POLθ</i> inhibitor sensitivity in BRCA2-deficient tumors, but are unlikely to be informative in other cancers.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Polymerase theta expression is correlated with proliferative capacity but not with DNA repair deficiency status in solid tumors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月20日

查看全文
  • Zsofia Sztupinszki,
  • Regina Fiam,
  • Orsolya Pipek,
  • Miklos Diossy,
  • Judit Börcsök,
  • Aurel Prosz,
  • Istvan Csabai,
  • Zoltan Szallasi

摘要

Polymerase theta (POLθ) inhibitors were developed to overcome resistance to PARP inhibitor treatment in homologous recombination (HR) deficient cancer. Biomarkers identifying PARP inhibitor-resistant cancer cases that specifically rely on POLθ activity for cancer cell survival will help to identify the sensitive patient population. From the TCGA RNAseq data, we determined POLθ expression levels, and from whole-exome and whole-genome sequencing data, we determined the number of POLθ-associated mutational signatures in solid tumors with various HR deficiency status. We found that POLθ expression levels did not differ significantly between HR-proficient and HR-deficient cancers. However, POLθ expression correlated strongly with proliferation-associated gene expression signatures and was predominantly observed in the S and G2/M phases of the cell cycle. POLθ-associated mutational signatures are correlated with POLθ expression levels only in BRCA2-deficient cancers. POLθ expression level and POLθ-associated mutational signatures may be indicative of POLθ inhibitor sensitivity in BRCA2-deficient tumors, but are unlikely to be informative in other cancers.