Two novel CYLD gene mutations in Chinese families with trichoepithelioma and a literature review of 16 families with trichoepithelioma reported in China

Liang, Yanhua; Gao, Min; Sun, Liangdan; Liu, L.J.; Cui, Yifan; Yang, Sen; Fan, Xing; Wang, J.; Xiao, Feng‐Li; Zhang, X.J.

doi:10.1111/j.1365-2133.2005.06960.x

Cited by 25 publications

(25 citation statements)

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“…[11][12][13][14][15][16] There are more than 20 germline CYLD mutations reported in MFT. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] An earlier study however suggested the role of another genetic locus on chromosome 9p21 in the etiopathogenesis of MFT. 26 Additionally, occasional studies focused on the PTCH gene 27 on chromosome 9q22.3, inasmuch as PTCH abnormalities had been recorded in sporadic basal cell carcinoma (BCC), the nevoid BCC syndrome, and trichoblastomas (including trichoepitheliomas).…”

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confidence: 92%

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

Kazakov

Vaněček²,

Zelger³

et al. 2011

The American Journal of Dermatopathology

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Multiple familial trichoepitheliomas (MFT) constitute an autosomally inherited syndrome possibly related to Brooke-Spiegler syndrome (BSS). Although some early studies suggested a role for the PTCH gene on chromosome 9q22.3 in the etiopathogenesis of MFT, recent studies of occasional patients with the MFT clinical phenotype identified mutations in the CYLD gene on chromosome 16q12-q13, a gene responsible for BSS. A systematic investigation of PTCH and CYLD mutations in patients with MFT has never been performed. Our main objective was to collect a reasonably large series of patients with MFT to (1) study the clinicopathological spectrum of the disease, (2) determine whether the PTCH gene is implicated in the pathogenesis of MFT, and if so (3) determine the relative frequency of CYLD and PTCH mutations, (4) establish if there may be any possible genotype-phenotype correlations, and (5) study the spectrum of somatic mutations. Clinical analysis including family histories, histopathological investigations, and molecular genetic studies were performed. There were 9 female and 7 male patients ranging in age from 11 to 63 years. They presented with multiple, small, discrete and sometimes confluent, skin-colored to pink, asymptomatic nodules preferentially located on the face, being especially prominent and confluent in the nasolabial folds and inner aspects of the eyebrows. A total of 66 conventional trichoepitheliomas (TEs) were studied microscopically. Aside from typical features of TE, some also exhibited variant morphological patterns including areas reminiscent of other benign adnexal neoplasms and melanocytic hyperplasia. In none of the 9 patients tested was a germline mutation of the PTCH gene identified. Germline CYLD mutations were detected in 6 of 13 patients tested (identical in 2 unrelated patients) including 2 novel mutations, whereas the remaining 7 individuals showed wild-type alleles. Two patients with germline wild-type CYLD showed, however, a somatic mutation in the gene (1 duplication, 1 substitution mutation). Neither CYLD nor PTCH germline mutations were found in the 5 patients in whom both genes were analyzed. MFT seems to be a phenotypic variant of BSS. The PTCH gene is rarely, if ever, involved in the pathogenesis of MFT. Absence of a germline mutation of the CYLD gene in cases harboring a somatic mutation may be explained by large deletions in the gene or by mutation in intronic sequences or in the promoter region. Considering our 5 patients with no mutation in either gene, the final possibility is that another, as yet undescribed gene (neither CYLD nor PTCH) is implicated in the pathogenesis of some patients with MFT.

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confidence: 92%

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

Kazakov

Vaněček²,

Zelger³

et al. 2011

The American Journal of Dermatopathology

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“…6 To our knowledge, this mutation has not been previously described. The known mutations of the CYLD gene are mostly located in the C-terminal portion.…”

Section: IIImentioning

confidence: 92%

“…When the second hit occurs in eccrineapocrine cells, the patients become susceptible to multiple cylindromas; in hair follicle cells, the patients exhibit susceptibility to multiple cylindromas or MFT. 6 Our study shows the importance of mutation screening of the CYLD gene in patients affected with FC and MFT as well as their relatives to identify early clinical manifestations. Analysis of control volunteers in this report confirms the role of this missense mutation as the cause of this syndrome.…”

Section: IIImentioning

confidence: 99%

“…The SHP-2 phosphatase plays several important roles in cellular physiologic function, mainly in cell proliferation, differentiation, migration, and adhesion. [6][7][8] This protein contains 2 main domains: a Cterminal protein-tyrosine phosphatase (PTP) domain involved in catalytic activity and 2 N-terminal Src homology 2 (SH2) domains interacting with the PTP domain, keeping it folded and inactive ( Figure 2). 3 To our knowledge, only 7 PTPN11 mutations have been reported in patients with LS, all of them in the PTP domain in exons 7 (Y279C and Y279S), 12 (T468M and A461T), and 13 …”

Section: Report Of a Casementioning

confidence: 99%

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A Novel Missense Mutation in the CYLD Gene in a Spanish Family With Multiple Familial Trichoepithelioma

España¹,

García-Amigot²,

Aguado³

et al. 2007

Arch Dermatol

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“…2 Our search of the literature revealed 51 germline CYLD gene mutations reported to date (Fig. 2,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Somatic CYLD mutations have rarely been investigated. 2,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Somatic CYLD mutations have rarely been investigated.…”

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confidence: 99%

Brooke-Spiegler Syndrome: Report of 10 Patients From 8 Families With Novel Germline Mutations

Šíma¹,

Vaněček²,

Kacerovská³

et al. 2010

Diagnostic Molecular Pathology

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Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms including spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma (cribriform trichoblastoma). BSS patients have various mutations in the CYLD gene, a tumor suppressor gene located on chromosome 16q. Our search of the literature revealed 51 germline CYLD mutations reported to date. Somatic CYLD mutations have rarely been investigated. We studied 10 patients from 8 families with BSS. Analysis of germline mutations of the CYLD gene was performed using either peripheral blood or nontumorous tissue. In addition, 19 formalin-fixed paraffin-embedded tumor samples were analyzed for somatic mutations, including loss of heterozygosity studies. A total of 38 tumors were available for histopathologic review. We have identified 8 novel germline mutations, all of which consisted of substitutions, deletions, and insertions/duplications and all except one led to premature stop codons. The substitution mutation in a single case was also predicted to disrupt protein function and seems causally implicated in tumor formation. We demonstrate for the first time that somatic events, loss of heterozygosity, or sequence mutations may differ among multiple neoplasms even of the same histologic type, occurring in the same patient.

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Two novel CYLD gene mutations in Chinese families with trichoepithelioma and a literature review of 16 families with trichoepithelioma reported in China

Cited by 25 publications

References 4 publications

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

A Novel Missense Mutation in the CYLD Gene in a Spanish Family With Multiple Familial Trichoepithelioma

Brooke-Spiegler Syndrome: Report of 10 Patients From 8 Families With Novel Germline Mutations

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