DNAJB1

Overview

DNAJB1 encodes a co-chaperone protein (DnaJ Heat Shock Protein Family Member B1) that assists HSP70 family chaperones. In oncology, DNAJB1 is best known for its role as the 5’ fusion partner in the DNAJB1-PRKACA rearrangement, which is pathognomonic for fibrolamellar hepatocellular carcinoma (FLC). This chromosomal deletion-derived fusion drives constitutive protein kinase A (PRKACA) activity and is the defining molecular event of this rare liver tumor subtype, which predominantly affects adolescents and young adults without underlying liver disease.

Alterations observed in the corpus

  • DNAJB1-PRKACA fusion was identified as pathognomonic for fibrolamellar hepatocellular carcinoma (FLC) in the msk_impact_2017 pan-cancer cohort (10,945 tumors across 62 tumor types profiled by MSK-IMPACT); the fusion was detected by both targeted DNA sequencing and orthogonal RNA fusion analysis PMID:28481359.
  • DNAJB1-PRKACA fusion is liver-only and specific to the fibrolamellar carcinoma (FLC) subtype of LIHC, corroborating Dinh et al. 2017; detected in the TCGA pan-cancer fusion landscape analysis PMID:29617662.

Cancer types (linked)

  • FLC: DNAJB1-PRKACA fusion is the defining molecular event of fibrolamellar hepatocellular carcinoma; classified as pathognomonic in the pan-cancer MSK-IMPACT cohort analysis PMID:28481359.

Co-occurrence and mutual exclusivity

  • The DNAJB1-PRKACA fusion defines FLC as a distinct entity from conventional HCC; the fusion typically arises from a ~400 kb intrachromosomal deletion on chromosome 19 and is mutually exclusive with the typical hepatocellular carcinoma drivers (PMID:28481359).

Therapeutic relevance

  • No approved targeted therapy specific to DNAJB1-PRKACA fusion is yet established; the constitutive PRKACA kinase activity represents a potential therapeutic target. Detection of this fusion by broad-panel sequencing (such as MSK-IMPACT) enables definitive molecular diagnosis and may guide enrollment in PRKACA-targeted trials PMID:28481359.

Open questions

  • The therapeutic implication of the DNAJB1-PRKACA fusion beyond diagnostic use remains under investigation; prospective data on targeted PRKACA inhibition in FLC are limited PMID:28481359.

Sources

This page was processed by crosslinker on 2026-05-15. - PMID:29617662

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