High frequency of FGFR3 mutations in adenoid seborrheic keratoses

被引:60
作者
Hafner, Christian
van Oers, Johanna M. M.
Hartmann, Arndt
Landthaler, Michael
Stoehr, Robert
Blaszyk, Hagen
Hofstaedter, Ferdinand
Zwarthoff, Ellen C.
Vogt, Thomas
机构
[1] Univ Regensburg, Dept Dermatol, D-93042 Regensburg, Germany
[2] Erasmus MC, Josephine Nefkens Inst, Dept Pathol, Rotterdam, Netherlands
[3] Univ Regensburg, Inst Pathol, D-8400 Regensburg, Germany
[4] Univ Regensburg, Dept Urol, D-8400 Regensburg, Germany
[5] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA
关键词
D O I
10.1038/sj.jid.5700422
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
FGFR3 germline mutations cause autosomal dominant skeletal disorders including achondroplasia, thanatophoric dysplasia, severe achondroplasia with developmental delay and acanthosis nigricans, and Crouzon syndrome. Somatic mutations of FGFR3 have been identified in bladder cancer, multiple myeloma, and other neoplasms. FGFR3 mutations have also been detected in 40% of seborrheic keratoses (SKs) of the hyperkeratotic and acanthotic subtype, which are very common benign skin tumors. Using a multiplex SNaPshot assay that covers 11 activating FGFR3 mutations, we investigated a series of 27 SKs of the adenoid subtype. Mutations were detected in 23 of 27 (85%) adenoid SKs. R248C mutations were the most frequent mutation type. In two SKs, the A393E mutation was found, which has not been described in acanthotic and hyperkeratotic SKs so far. Three adenoid SKs displayed two simultaneous FGFR3 mutations. Adenoid SKs seem to be characterized by a higher frequency of FGFR3 mutations than hyperkeratotic and acanthotic SKs. The mechanism for the high rate of somatic FGFR3 mutations in these benign skin tumors remains elusive, but UV light exposure may play a potential role, especially in the R248C mutations.
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页码:2404 / 2407
页数:4
相关论文
共 13 条
  • [1] FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies
    Chen, J
    Lee, BH
    Williams, IR
    Kutok, JL
    Mitsiades, CS
    Duclos, N
    Cohen, S
    Adelsperger, J
    Okabe, R
    Coburn, A
    Moore, S
    Huntly, BJP
    Fabbro, D
    Anderson, KC
    Griffin, JD
    Gilliland, DG
    [J]. ONCOGENE, 2005, 24 (56) : 8259 - 8267
  • [2] No chromosomal imbalances in seborrheic keratoses detectable by comparative genomic hybridization
    Hallermann, C
    Gunawan, B
    Bertsch, HP
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2004, 123 (06) : 1204 - 1205
  • [3] No evidence of somatic FGFR3 mutation in various types of carcinoma
    Karoui, M
    Hofmann-Radvanyi, H
    Zimmermann, U
    Couvelard, A
    Degott, C
    Faridoni-Laurens, L
    Ahomadegbe, JC
    Gazzeri, S
    Brambilla, E
    Clerici, T
    Charbonnier, P
    Tresallet, C
    Mitry, E
    Penna, C
    Rougier, P
    Boileau, C
    Thiery, JP
    Nordlinger, B
    Franc, B
    Radvanyi, F
    [J]. ONCOGENE, 2001, 20 (36) : 5059 - 5061
  • [4] Seborrheic keratosis in the Korean males: causative role of sunlight
    Kwon, OS
    Hwang, EJ
    Bae, JH
    Park, HE
    Lee, JC
    Youn, JI
    Chung, JH
    [J]. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE, 2003, 19 (02) : 73 - 80
  • [5] Cell responses to FGFR3 signalling:: growth, differentiation and apoptosis
    L'Hôte, CGM
    Knowles, MA
    [J]. EXPERIMENTAL CELL RESEARCH, 2005, 304 (02) : 417 - 431
  • [6] Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans
    Logié, A
    Dunois-Lardé, C
    Rosty, C
    Levrel, O
    Blanche, M
    Ribeiro, A
    Gasc, JM
    Jorcano, J
    Werner, S
    Sastre-Garau, X
    Thiery, JP
    Radvanyi, F
    [J]. HUMAN MOLECULAR GENETICS, 2005, 14 (09) : 1153 - 1160
  • [7] Clonal nature of seborrheic keratosis demonstrated by using the polymorphism of the human androgen receptor locus as a marker
    Nakamura, H
    Hirota, S
    Adachi, S
    Ozaki, K
    Asada, H
    Kitamura, Y
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2001, 116 (04) : 506 - 510
  • [8] Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia
    Naski, MC
    Wang, Q
    Xu, JS
    Ornitz, DM
    [J]. NATURE GENETICS, 1996, 13 (02) : 233 - 237
  • [9] Perez-Oliva N, 1990, Med Cutan Ibero Lat Am, V18, P70
  • [10] The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: The achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans
    Vajo, Z
    Francomano, CA
    Wilkin, DJ
    [J]. ENDOCRINE REVIEWS, 2000, 21 (01) : 23 - 39