Enhanced lymphocyte interferon (IFN)-γ responses in a PTEN mutation-negative Cowden disease kindred.

R. Stevenson, A. Fatehullah, Victoria Bingham, Ravi Deevi, Ishaan Jagan, Alexandra Irvine, Marilyn Armstrong, Patrick Morrison, I. Dimmick, R. Stewart, Frederick Campbell

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Identification of immune modifiers of inherited cancer syndromes may provide a rationale for preventive therapy. Cowden disease (CD) is a genetically heterogeneous inherited cancer syndrome that arises predominantly from germline phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutation and increased phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) signalling. However, many patients with classic CD diagnostic features are mutation-negative for PTEN (PTEN M-Neg). Interferon (IFN)-gamma can modulate the PI3K/mTOR pathway, but its association with PTEN M-Neg CD remains unclear. This study assessed IFN-gamma secretion by multi-colour flow cytometry in a CD kindred that was mutation-negative for PTEN and other known susceptibility genes. Because IFN-gamma responses may be regulated by killer cell immunoglobulin-like receptors (KIR) and respective human leucocyte antigen (HLA) ligands, KIR/HLA genotypes were also assessed. Activating treatments induced greater IFN-gamma secretion in PTEN M-Neg CD peripheral blood lymphocytes versus healthy controls. Increased frequency of activating KIR genes, potentially activating KIR/HLA compound genotypes and reduced frequency of inhibitory genotypes, were found in the PTEN M-Neg CD kindred. Differences of IFN-gamma secretion were observed among PTEN M-Neg CD patients with distinct KIR/HLA compound genotypes. Taken together, these findings show enhanced lymphocyte secretion of IFN-gamma that may influence the PI3K/mTOR CD causal molecular pathway in a PTEN mutation-negative CD kindred.
Original languageEnglish
Pages (from-to)202-210
Number of pages9
JournalClinical and Experimental Immunology
Issue number2
Publication statusPublished - May 2011

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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