APOBEC3B

Overview

APOBEC3B (Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3B) encodes a cytidine deaminase that converts cytosine to uracil in single-stranded DNA, generating TpC-context mutations (C→T and C→G). It is highly expressed in multiple cancer types and is a major driver of the APOBEC mutational signature (COSMIC SBS2 and SBS13), contributing to tumor heterogeneity and resistance evolution.

Alterations observed in the corpus

  • Highly expressed across all muscle-invasive bladder carcinomas (BLCA, n=131); the dominant source of the TpC mutational signature representing 51% of all mutations in the TCGA bladder cohort; APOBEC3B expression correlates with mutational burden in urothelial carcinoma PMID:24476821
  • Up-regulated in ESCC tumors; implicated as the cytidine deaminase responsible for the trinucleotide mutational signature observed across 139 paired ESCC samples PMID:24686850
  • Elevated mRNA in chromophobe RCC vs normal kidney; APOBEC mutational signature enriched in kataegis-bearing ChRCC cases PMID:25155756
  • APOBEC3B RTCA mutagenesis significantly enriched (P=0.0395) in post-chemotherapy urothelial carcinoma tumors, implicated in chemotherapy-driven mutational editing via increased ssDNA availability during repair PMID:27749842
  • APOBEC3B mutational activity (signatures 2 and 13) nearly doubled in HR+/HER2- metastatic breast cancer vs primary TCGA samples — linked to subclonal mutation acquisition under therapy, suggesting a generalized resistance mechanism PMID:28027327
  • APOBEC3B mutational signature modestly enriched at the NOL10 locus in CPGEA and TCGA PRAD vs. genome-wide background, suggesting ectopic APOBEC mutagenesis as a complementary somatic contributor to NOL10 deregulation in prostate cancer PMID:28927585
  • Expression correlates with APOBEC-signature mutation load in MIBC; APOBEC3A/3B together account for 67% of all SNVs in the TCGA MIBC cohort (n=412), with their expression as the dominant mutagenic source PMID:28988769

Cancer types (linked)

  • Bladder urothelial carcinoma (BLCA): APOBEC3B identified as likely driver of TpC→(T/G) mutational signature comprising 51% of all somatic mutations in 131 chemotherapy-naive muscle-invasive tumors; high APOBEC3B expression observed in all tumours of the TCGA cohort PMID:24476821

Co-occurrence and mutual exclusivity

  • APOBEC-mediated mutagenesis is pervasive across BLCA tumor clusters and is not exclusive to any single mRNA expression subtype; the mean mutation rate in this cohort (7.7/Mb) is partly attributable to APOBEC activity PMID:24476821

Therapeutic relevance

  • APOBEC3B expression is not itself an actionable target but serves as a biomarker for high mutational burden; the resulting high neoantigen load may enhance immune checkpoint inhibitor response in BLCA PMID:24476821

Open questions

  • Whether APOBEC3B or other APOBEC family members (e.g., APOBEC3A) are the predominant source of TpC mutations in bladder cancer is not resolved by this study, which measures expression but does not perform deaminase activity assays PMID:24476821

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:24686850

This page was processed by wiki-cli on 2026-05-11. - PMID:25155756

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