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Normal Function
The CYLD gene provides instructions for making an enzyme that helps regulate numerous signaling pathways, many of which are involved in cell growth. These pathways include nuclear factor-kappa-B (NF-KB), Wnt, c-Jun N-terminal kinase (JNK), transforming growth factor beta-1 (TGFB1), and Notch signaling pathways. By regulating these signaling pathways, the CYLD enzyme helps cells respond properly to signals that promote cell growth and division (proliferation) or self-destruction (apoptosis), as necessary. By regulating signals that control cell growth, the CYLD enzyme acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.
Health Conditions Related to Genetic Changes
CYLD cutaneous syndrome
More than 100 mutations in the CYLD gene have been identified in individuals with CYLD cutaneous syndrome. This condition is characterized by multiple noncancerous (benign) tumors that develop in structures associated with the skin (skin appendages), such as hair follicles. More than one type of skin tumor often develops, including benign growths called cylindromas, spiradenomas, and trichoepitheliomas. Cylindromas were previously thought to derive from sweat glands, but they are now generally believed to begin in hair follicles and often appear on the scalp. Spiradenomas are related to cylindromas and it is common to find features of both of these benign growths in a single tumor. Trichoepitheliomas arise from hair follicles and typically develop on the skin around the nose and upper lip.
Most people with CYLD cutaneous syndrome are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD enzyme from the altered copy of the gene. However, enough enzyme is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation that alters or removes (deletes) the normal copy of the CYLD gene must occur. The second mutation, called a somatic mutation, occurs during a person's lifetime and is found in only certain cells in the body.
When both copies of the CYLD gene are mutated, the cell cannot produce any functional CYLD enzyme. The loss of this enzyme impairs the regulation of signaling pathways, allowing the cell to grow and divide in an uncontrolled way to form a tumor. In people with CYLD cutaneous syndrome, somatic CYLD gene mutations typically occur in multiple types of cells in the skin over an affected person's lifetime, leading to the growth of several types of skin appendage tumors.
More About This Health ConditionCancers
Somatic mutations of the CYLD gene have also been found in certain cancers, including cancer of the bone marrow (multiple myeloma), salivary glands, kidneys, liver, colon, or uterus. These mutations result in a reduction of CYLD gene activity and likely impairs the tumor suppressor function of the CYLD enzyme, allowing cells to grow and divide in an uncontrolled way and become cancerous.
Other Names for This Gene
- BRSS
- CDMT
- CYLD1
- CYLD_HUMAN
- CYLDI
- EAC
- HSPC057
- KIAA0849
- MFT
- MFT1
- SBS
- TEM
- USPL2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Alameda JP, Fernandez-Acenero MJ, Moreno-Maldonado R, Navarro M, Quintana R, Page A, Ramirez A, Bravo A, Casanova ML. CYLD regulates keratinocyte differentiation and skin cancer progression in humans. Cell Death Dis. 2011 Sep 8;2(9):e208. doi: 10.1038/cddis.2011.82. Citation on PubMed or Free article on PubMed Central
- Andersson MK, Kolby L, Nilsson JA, Stenman G. Clinical, genetic and experimental studies of the Brooke-Spiegler (CYLD) skin tumor syndrome. J Plast Surg Hand Surg. 2019 Apr;53(2):71-75. doi: 10.1080/2000656X.2018.1547736. Epub 2019 Jan 24. Citation on PubMed
- Blake PW, Toro JR. Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling. Hum Mutat. 2009 Jul;30(7):1025-36. doi: 10.1002/humu.21024. Citation on PubMed or Free article on PubMed Central
- Dubois A, Rajan N. CYLD Cutaneous Syndrome. 2020 Apr 16. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK555820/ Citation on PubMed
- Dubois A, Wilson V, Bourn D, Rajan N. CYLD GeneticTesting for Brooke-Spiegler Syndrome, Familial Cylindromatosis and Multiple Familial Trichoepitheliomas. PLoS Curr. 2015 Feb 19;7:ecurrents.eogt.45c4e63dd43d62e12228cc5264d6a0db. doi: 10.1371/currents.eogt.45c4e63dd43d62e12228cc5264d6a0db. Citation on PubMed
- Massoumi R. CYLD: a deubiquitination enzyme with multiple roles in cancer. Future Oncol. 2011 Feb;7(2):285-97. doi: 10.2217/fon.10.187. Citation on PubMed
- Rajan N, Ashworth A. Inherited cylindromas: lessons from a rare tumour. Lancet Oncol. 2015 Sep;16(9):e460-e469. doi: 10.1016/S1470-2045(15)00245-4. Citation on PubMed
- Rito M, Mitani Y, Bell D, Mariano FV, Almalki ST, Pytynia KB, Fonseca I, El-Naggar AK. Frequent and differential mutations of the CYLD gene in basal cell salivary neoplasms: linkage to tumor development and progression. Mod Pathol. 2018 Jul;31(7):1064-1072. doi: 10.1038/s41379-018-0018-6. Epub 2018 Feb 20. Citation on PubMed
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