The cylindromatosis (CYLD) gene and head and neck tumorigenesis

Abstract

Germline CYLD mutation is associated with the development of a rare inheritable syndrome, called the CYLD cutaneous syndrome. Patients with this syndrome are distinctly presented with multiple tumors in the head and neck region, which can grow in size and number over time. Some of these benign head and neck tumors can turn into malignancies in some individuals. CYLD has been identified to be the only tumor suppressor gene reported to be associated with this syndrome thus far. Here, we summarize all reported CYLD germline mutations associated with this syndrome, as well as the reported paired somatic CYLD mutations of the developed tumors. Interestingly, whole-exome sequencing (WES) studies of multiple cancer types also revealed CYLD mutations in many human malignancies, including head and neck cancers and several epithelial cancers. Currently, the role of CYLD mutations in head and neck carcinogenesis and other cancers is poorly defined. We hope that this timely review of recent findings on CYLD genetics and animal models for oncogenesis can provide important insights into the mechanism of head and neck tumorigenesis.

Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication

“…CYLD works as a tumor suppressor in multiple cancers 40 , 41 . Downregulation of CYLD is correlated with tumor initiation, development, metastasis, and resistance to treatment 16 , 42 – 44 .However, the expression and function of CYLD in NPC is still unclear.…”

Brooke–Spiegler Syndrome: Two Patients From a Turkish Family With Multiple Familial Trichoepithelioma

“…The CYLD is a tumor suppressor gene that plays a key role on regulation of NF-kB signaling pathway. 1 In this study, we present 2 cases in a Turkish family with MFT carrying the CYLD mutation and aim to discuss with the literature.…”

Genomic Landscapes of EBV-Associated Nasopharyngeal Carcinoma vs. HPV-Associated Head and Neck Cancer

“…Over 40% of microdissected EBV(+) NPC tumors were found to harbor genetic aberrations (including translocation, tandem duplication, homozygous deletion and mutation) of negative regulators of NF-κB pathways, which include: CYLD (18.6%), TRAF3 (17.5%), NFKBIA (6.7%) and NLRC5 (4.8%) [ 43 ]. CYLD is a tumor suppressor gene, when germline mutated, it can contribute to a rare form of inherited syndrome called the CYLD (cylindromatosis) cutaneous syndrome with clinical manifestation of multiple benign tumors in the head and neck region at early age [ 59 ]. CYLD is a deubiquitinase that drives the degradation of multiple regulators of the NF-κB pathway [ 43 ].…”