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Updated: Mar 20, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
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Microsatellite instability derived JAK1 frameshift mutations are associated with tumor immune evasion in endometrioid

Ellen Stelloo1, Marco A Versluis2, Hans W Nijman2

  • 1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Oncotarget
|May 24, 2016
PubMed

Insights

JAK1 frameshift mutations are common in microsatellite unstable endometrial cancers (ECs). These mutations impair antigen presentation pathways, potentially aiding cancer immune evasion, but do not affect patient survival.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Microsatellite instability (MSI) is a hallmark of certain cancers, including endometrial cancer (EC).
  • JAK1 mutations have been implicated in cancer development and immune response modulation.

Purpose of the Study:

  • To investigate the frequency and functional role of JAK1 mutations in MSI endometrial cancers.
  • To determine the association between JAK1 mutations, immune evasion, and patient prognosis.

Main Methods:

  • Analysis of JAK1 mutations and microsatellite instability in 181 EC samples.
  • Assessment of antigen presentation pathway components (LMP7, TAP1, HLA class I) and CD8+ T-cell infiltration in MSI ECs.
  • Validation using TCGA RNAseq data and assessment of prognostic significance in an additional 198 MSI ECs.

Main Results:

  • JAK1 mutations were found in 35% of MSI ECs.
  • JAK1 mutant MSI ECs exhibited impaired upregulation of LMP7 and HLA class I, suggesting compromised antigen presentation.
  • No significant association was found between JAK1 mutations and patient survival (10-year recurrence-free rates: 84% for wildtype vs. 77% for mutant).

Conclusions:

  • JAK1 mutations are frequent in MSI endometrial cancers and are associated with impaired antigen presentation pathway components, potentially contributing to immune evasion.
  • JAK1 mutations in this context do not appear to have a significant impact on patient prognosis or survival.
Keywords:
HLA class IJAK1antigen presentation machineryendometrial cancermicrosatellite instability

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