PPP1R1B
Overview
PPP1R1B (also known as DARPP-32, dopamine- and cAMP-regulated neuronal phosphoprotein) encodes a protein phosphatase-1 regulatory subunit that integrates dopaminergic and glutamatergic signaling in neuronal contexts. In cancer, PPP1R1B is located on chromosome 17q12, adjacent to ERBB2, and has been identified as a fusion partner with ERBB2 in settings where local genomic instability — potentially induced by HPV integration — produces rearrangements between neighboring genes.
Alterations observed in the corpus
- PPP1R1B is a fusion partner of ERBB2 in 4 TCGA samples; three of the four ERBB2-fusion samples had HPV integration within 1 Mb of ERBB2, and PPP1R1B and IKZF3 are genomic neighbors of ERBB2, suggesting these fusions arise from local instability potentially induced by viral integration PMID:29617662.
Cancer types (linked)
- BRCA — ERBB2–PPP1R1B fusions contextualized as a distinct mechanism of HER2 dysregulation, compared with canonical trastuzumab-targetable HER2 amplification PMID:29617662.
- LIHC — among cancer types where local chromosomal instability at the 17q12 locus has been observed in the pan-cancer fusion landscape PMID:29617662.
Co-occurrence and mutual exclusivity
- ERBB2 fusion partners PPP1R1B and IKZF3 share proximity to ERBB2 on 17q12, consistent with local rearrangement rather than distant translocation; HPV integration co-occurs in 3 of 4 ERBB2-fusion samples PMID:29617662.
Therapeutic relevance
- ERBB2 fusions involving PPP1R1B represent a potentially actionable HER2 dysregulation mechanism distinct from amplification; trastuzumab is the canonical ERBB2-amplification therapy, but therapeutic evaluation of ERBB2 fusions specifically has not yet been reported in this dataset PMID:29617662.
Open questions
- Whether ERBB2–PPP1R1B fusions produce a constitutively active or overexpressed HER2 kinase amenable to standard HER2-targeted therapies remains untested in this pan-cancer series.
Sources
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