Journal article

Human perforin mutations and susceptibility to multiple primary cancers

Joseph A Trapani, Kevin YT Thia, Miles Andrews, Ian D Davis, Craig Gedye, Philip Parente, Suzanne Svobodova, Jenny Chia, Kylie Browne, Ian G Campbell, Wayne A Phillips, Ilia Voskoboinik, Jonathan S Cebon



Loss-of-function mutations in the gene coding for perforin (PRF1) markedly reduce the ability of cytotoxic T lymphocytes and natural killer cells to kill target cells, causing immunosuppression and impairing immune regulation. In humans, nearly half of the cases of type 2 familial hemophagocytic lymphohistiocytosis are due to bi-allelic PRF1 mutations. The partial inactivation of PRF1 due to mutations that promote protein misfolding or the common hypomorphic allele coding for the A91V substitution have been associated with lymphoid malignancies in childhood and adolescence. To investigate whether PRF1 mutations also predispose adults to cancer, we genotyped 566 individuals diagnosed with mel..

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Funding Acknowledgements

We acknowledge support from the National Health and Medical Research Council (NHMRC), Melanoma Research Alliance (MRA), Victorian Cancer Agency (VCA), the Victorian State Government Operational Infrastructure Support Program and the NHMRC Independent Research Institutes Infrastructure Support Scheme.