Skip to main content
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 2001 Sep;54(9):689–692. doi: 10.1136/jcp.54.9.689

Loss of heterozygosity at cylindromatosis gene locus, CYLD, in sporadic skin adnexal tumours

N Leonard 1, R Chaggar 1, C Jones 1, M Takahashi 1, A Nikitopoulou 1, S Lakhani 1
PMCID: PMC1731526  PMID: 11533075

Abstract

Aim—The gene for familial cylindromatosis (CYLD) has been localised to chromosome 16q, and has recently been cloned. Loss of heterozygosity (LOH) at 16q has also been demonstrated in sporadic cylindromas. The aim of this study was to investigate whether CYLD plays a role in the development of other skin appendage tumours.

Methods—A total of 55 cases of skin adnexal tumours, comprising 12 different types, and a control group of 14 squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) were studied. Three microsatellites (D16S407 (16p), D16S304 (16q), and D16S308 (16q)) were analysed for LOH after microdissection from paraffin wax embedded sections using laser capture microdissection.

Results—In keeping with previous data, a proportion of cylindromas exhibited LOH at markers on 16q, but not at 16p. The skin adnexal tumours showing a similar pattern included apocrine hydrocystomas, eccrine spiradenomas, and sebaceous adenoma. One case of syringoma showed LOH at 16q, and a further case at 16p, but not 16q. One case of eccrine hydrocystoma showed loss at 16p, but not 16q. The remaining tumours were either negative or non-informative. All tumours in the control group were either negative or non-informative, except for a single case of BCC showing LOH at 16q.

Conclusion—CYLD may be involved in the development of skin adnexal tumours other than cylindromas.

Key Words: cylindromatosis locus CYLD • loss of heterozygosity • skin adnexal tumours

Full Text

The Full Text of this article is available as a PDF (209.6 KB).

graphic file with name 00188.f1.jpg

Figure 1 (A) Characteristic morphology of cylindroma, showing lobules of basophilic epithelial cells, surrounded by thick hyaline membranes (haematoxylin and eosin stain; original magnification, x200). (B) Loss of heterozygosity at 16q (D16S308). There is an imbalance at the 156 bp allele (allele ratio of 0.2) compared with the normal DNA.

graphic file with name 00188.f2.jpg

Figure 2 (A) Histology of sebaceous adenoma (haematoxylin and eosin stain; original magnification, x200). (B) Loss of heterozygosity at 16q (D16S304). There is a loss of the 151 bp allele (allele ratio of 0).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Biernat W., Kordek R., Woźniak L. Over-expression of p53 protein as an indicator of the malignant transformation in spiradenoma. Histopathology. 1995 May;26(5):439–443. doi: 10.1111/j.1365-2559.1995.tb00251.x. [DOI] [PubMed] [Google Scholar]
  2. Biggs P. J., Chapman P., Lakhani S. R., Burn J., Stratton M. R. The cylindromatosis gene (cyld1) on chromosome 16q may be the only tumour suppressor gene involved in the development of cylindromas. Oncogene. 1996 Mar 21;12(6):1375–1377. [PubMed] [Google Scholar]
  3. Biggs P. J., Wooster R., Ford D., Chapman P., Mangion J., Quirk Y., Easton D. F., Burn J., Stratton M. R. Familial cylindromatosis (turban tumour syndrome) gene localised to chromosome 16q12-q13: evidence for its role as a tumour suppressor gene. Nat Genet. 1995 Dec;11(4):441–443. doi: 10.1038/ng1295-441. [DOI] [PubMed] [Google Scholar]
  4. Bignell G. R., Warren W., Seal S., Takahashi M., Rapley E., Barfoot R., Green H., Brown C., Biggs P. J., Lakhani S. R. Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet. 2000 Jun;25(2):160–165. doi: 10.1038/76006. [DOI] [PubMed] [Google Scholar]
  5. Chan E. F., Gat U., McNiff J. M., Fuchs E. A common human skin tumour is caused by activating mutations in beta-catenin. Nat Genet. 1999 Apr;21(4):410–413. doi: 10.1038/7747. [DOI] [PubMed] [Google Scholar]
  6. Cohen P. R., Kohn S. R., Davis D. A., Kurzrock R. Muir-Torre syndrome. Dermatol Clin. 1995 Jan;13(1):79–89. [PubMed] [Google Scholar]
  7. Dijkhuizen T., van den Berg E., Nikkels P. G., Hoekstra H. J., de Jong B. Cytogenetics of a case of eccrine spiradenoma. Hum Pathol. 1992 Sep;23(9):1085–1087. doi: 10.1016/0046-8177(92)90274-7. [DOI] [PubMed] [Google Scholar]
  8. Eng C. Genetics of Cowden syndrome: through the looking glass of oncology. Int J Oncol. 1998 Mar;12(3):701–710. doi: 10.3892/ijo.12.3.701. [DOI] [PubMed] [Google Scholar]
  9. Fend F., Raffeld M. Laser capture microdissection in pathology. J Clin Pathol. 2000 Sep;53(9):666–672. doi: 10.1136/jcp.53.9.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ferrándiz C., Campo E., Baumann E. Dermal cylindromas (turban tumour) and eccrine spiradenomas in a patient with membranous basal cell adenoma of the parotid gland. J Cutan Pathol. 1985 Feb;12(1):72–79. doi: 10.1111/j.1600-0560.1985.tb00432.x. [DOI] [PubMed] [Google Scholar]
  11. Gailani M. R., Bale S. J., Leffell D. J., DiGiovanna J. J., Peck G. L., Poliak S., Drum M. A., Pastakia B., McBride O. W., Kase R. Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9. Cell. 1992 Apr 3;69(1):111–117. doi: 10.1016/0092-8674(92)90122-s. [DOI] [PubMed] [Google Scholar]
  12. Harada H., Hashimoto K., Ko M. S. The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J Invest Dermatol. 1996 Jul;107(1):41–43. doi: 10.1111/1523-1747.ep12297860. [DOI] [PubMed] [Google Scholar]
  13. Holmberg E., Rozell B. L., Toftgård R. Differential allele loss on chromosome 9q22.3 in human non-melanoma skin cancer. Br J Cancer. 1996 Jul;74(2):246–250. doi: 10.1038/bjc.1996.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lakhani S. R., Chaggar R., Davies S., Jones C., Collins N., Odel C., Stratton M. R., O'Hare M. J. Genetic alterations in 'normal' luminal and myoepithelial cells of the breast. J Pathol. 1999 Dec;189(4):496–503. doi: 10.1002/(SICI)1096-9896(199912)189:4<496::AID-PATH485>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  15. Quinn A. G., Sikkink S., Rees J. L. Basal cell carcinomas and squamous cell carcinomas of human skin show distinct patterns of chromosome loss. Cancer Res. 1994 Sep 1;54(17):4756–4759. [PubMed] [Google Scholar]
  16. Quinn A. G., Sikkink S., Rees J. L. Delineation of two distinct deleted regions on chromosome 9 in human non-melanoma skin cancers. Genes Chromosomes Cancer. 1994 Dec;11(4):222–225. doi: 10.1002/gcc.2870110404. [DOI] [PubMed] [Google Scholar]
  17. Shapiro P. E., Kopf A. W. Familial multiple desmoplastic trichoepitheliomas. Arch Dermatol. 1991 Jan;127(1):83–87. [PubMed] [Google Scholar]
  18. Takata M., Quinn A. G., Hashimoto K., Rees J. L. Low frequency of loss of heterozygosity at the nevoid basal cell carcinoma locus and other selected loci in appendageal tumors. J Invest Dermatol. 1996 May;106(5):1141–1144. doi: 10.1111/1523-1747.ep12340190. [DOI] [PubMed] [Google Scholar]
  19. Verhoef S., Schrander-Stumpel C. T., Vuzevski V. D., Tempelaars A., Jansen L. A., Malfeyt G. A., Ceelen T. L., Lindhout D., Halley D. J., van den Ouweland A. M. Familial cylindromatosis mimicking tuberous sclerosis complex and confirmation of the cylindromatosis locus, CYLD1, in a large family. J Med Genet. 1998 Oct;35(10):841–845. doi: 10.1136/jmg.35.10.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yokota J., Sugimura T. Multiple steps in carcinogenesis involving alterations of multiple tumor suppressor genes. FASEB J. 1993 Jul;7(10):920–925. doi: 10.1096/fasebj.7.10.8344488. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES