Germline hemizygous deletion of CDKN2A-CDKN2B locus in a patient presenting with Li-Fraumeni syndrome.

ABSTRACT: Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome usually associated with TP53 germline alterations. Its genetic basis in TP53 wild-type pedigrees is less understood. Using whole-genome sequencing, we identified a germline hemizygous deletion ablating CDKN2A-CDKN2B in a TP53 wild-type patient presenting with high-grade sarcoma, laryngeal squamous cell carcinoma and a family history suggestive of LFS. Patient-derived cells demonstrated reduced basal gene and protein expression of the CDKN2A-encoded tumour suppressors p14^ARF and p16^INK4A with concomitant decrease in p21 and faster cell proliferation, implying potential deregulation of p53-mediated cell cycle control. Review of 13 additional patients with pathogenic

SUBMITTER: Chan SH 

PROVIDER: S-EPMC5685299 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature