Pinpointing a potential role for CLEC12B in cancer predisposition through familial exome sequencing

Abstract

Predisposition to cancer is only partly understood, and thus, the contribution of still undiscovered cancer predisposing variants necessitates further research. In search of such variants, we performed exome sequencing on the germline DNA of a family with two children affected by ganglioneuroma and neuroblastoma. Applying stringent selection criteria, we identified a potential deleterious, missense mutation in CLEC12B, coding for a lectin C‐type receptor that is predicted to regulate immune function. Although further screening in a larger population and functional characterization is needed, we propose CLEC12B as a candidate cancer predisposition gene.

C‐type lectin receptors of the Dectin‐1 cluster: Physiological roles and involvement in disease

“…In the context of disease, CLEC‐12B is upregulated along with other immunosuppressive genes during the transition from the acute to asymptomatic stage during HIV infections, and it is part of a set of negative regulators upregulated in Behçet's Syndrome . The presence of a polymorphism in CLEC12B , which may affect the secondary structure of the C‐type lectin‐like domain, has been linked in one family with predisposition to childhood cancer . Suggestively, both SHP‐1 and SHP‐2 have also been linked to cancer, including melanomas, but more work is required to define the physiological role of CLEC‐12B.…”