A mutation in the hydin gene has been recently described as one possible mecha-nism leading to lethal congenital hydrocephalus in mice, and a similar defect is pro-posed to be involved in an autosomal recessive form of hydrocephalus in human. Here, we report for the first time on the cancer association and immunogenicity of two hydin variants in humans. One is a previously-described sequence derived from the chromosome 1 gene copy, i.e. KIAA1864. The second is encoded by a novel alternative transcript originating from the chromosome 16 which we identified by im-munoscreening of a testis-derived cDNA expression library with sera of patients with colorectal cancer and that we called MO-TES391. Both variants are targeted by IgG antibodies in a significant subset of cancer patients but only rarely in healthy donors. Moreover, we identify HLA-A*0201-restricted sequences derived from MO-TES391 and KIAA1864 which are specifically recognized by human cytotoxic CD8+ T cells. Taken together, these results suggest frequent and coordinated adaptive immune responses against HYDIN variants in cancer patients and propose HYDIN as a novel cancer associated antigen.
- Received June 20, 2013.
- Accepted June 24, 2013.
- Copyright © 2013, American Association for Cancer Research.