FGFR3 mutations and the skin: Report of a patient with a FGFR3 gene mutation, acanthosis nigricans, hypochondroplasia and hyperinsulinemia and review of the literature

Dermatology

Volumn 220, Issue 4, 2010, Pages 297-305

  Blomberg, M ^a,d   Jeppesen, E M ^b   Skovby, F ^c   Benfeldt, E ^a  

^a GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^b GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

^d NONE   (Denmark)

Author keywords

Acanthosis nigricans; Fibroblast growth factor receptor type 3; Genes; Hyperinsulinemia; Hypochondroplasia; Mutation

Indexed keywords

C PEPTIDE; FIBROBLAST GROWTH FACTOR RECEPTOR 3; GLUCOSE; GONADORELIN; GROWTH HORMONE; HUMAN GROWTH HORMONE; KI 67 ANTIGEN; METFORMIN; SALICYLIC ACID; WHITE PETROLATUM; FGFR3 PROTEIN, HUMAN; GLUCOSE BLOOD LEVEL;

ACANTHOSIS NIGRICANS; ADOLESCENT; BECKER NEVUS; BENIGN SKIN TUMOR; BONE DYSPLASIA; CASE REPORT; DNA DETERMINATION; DRUG WITHDRAWAL; EXON; FEMALE; GENE MUTATION; HUMAN; HYPERINSULINEMIA; HYPERKERATOSIS; HYPERPIGMENTATION; HYPOCHONDROPLASIA; KARYOTYPE 46,XX; PATHOGENESIS; POINT MUTATION; PRIORITY JOURNAL; PSYCHOMOTOR DISORDER; REVIEW; SEBORRHEIC KERATOSIS; SKIN DEFECT; SOMATIC MUTATION; SQUAMOUS CELL CARCINOMA; BLOOD; DRUG EFFECTS; DWARFISM; GENETICS; GLUCOSE BLOOD LEVEL; HYPERINSULINISM; PATHOLOGY;

ACANTHOSIS NIGRICANS; ADOLESCENT; BLOOD GLUCOSE; C-PEPTIDE; DWARFISM; FEMALE; GONADOTROPIN-RELEASING HORMONE; HUMAN GROWTH HORMONE; HUMANS; HYPERINSULINISM; KERATOSIS, SEBORRHEIC; METFORMIN; POINT MUTATION; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 3;

EID: 77954242901     PISSN: 10188665     EISSN: None     Source Type: Journal    
DOI: 10.1159/000297575     Document Type: Review

References (54)

1. Delezoide AL, Benoist-Lasselin C, Legeai- Mallet L, Le Merrer M, Munnich A, Vekemans M, Bonaventure J: Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal ossification. Mech Dev 1998; 77: 19-30.
2. Deng C, Wynshaw-Boris A, Zhou F, Kuo A, Leder P: Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell 1996; 84: 911-921.
3. Bellus GA, Bamshad MJ, Przylepa KA, Dorst J, Lee RR, Hurko O, Jabs EW, Curry CJ, Wilcox WR, Lachman RS, Rimoin DL, Francomano CA: Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. Am J Med Genet 1999; 85: 53-65.
4. Baker KM, Olson DS, Harding CO, Pauli RM: Long-term survival in typical thanatophoric dysplasia type 1. Am J Med Genet 1997; 70: 427-436.
5. Arnaud-Lopez L, Fragoso R, Mantilla-Capacho J, Barros-Núñez P: Crouzon with acanthosis nigricans. Further delineation of the syndrome. Clin Genet 2007; 72: 405-410.
6. Van Esche H, Fryns JE: Acanthosis nigricans in a boy with achondroplasia due to the classical Gly380Arg mutation in FGFR3. Genet Couns 2004; 15: 375-377.
7. Castro-Feijoo L, Loidi L, Vidal A, Parajes S, Roson E, Alvarez A, Cabanas P, Barreiro J, Alonso A, Dominguez F, Pombo M: Hypochondroplasia and acanthosis nigricans: a new syndrome due to the p.Lys650Thr mutation in the fibroblast growth factor receptor 3 gene? Eur J Endocrinol 2008; 159: 243-249.
8. Berk DR, Spector EB, Bayliss SJ: Familial acanthosis nigricans due to K650T FGFR3 mutation. Arch Dermatol 2007; 143: 1153-1156.
9. Leroy JG, Nuytinck L, Lambert J, Naeyaert JM, Mortier GR: Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene. Am J Med Genet A 2007; 143A:3144-3149.
10. Logie A, Dunois-Larde C, Rosty C, Levrel O, Blanche M, Ribeiro A, Gasc JM, Jorcano J, Werner S, Sastre-Garau X, Thiery JP, Radvanyi F: Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans. Hum Mol Genet 2005; 14: 1153-1160.
11. Guran T, Turan S, Akcay T, Bereket A: Significance of acanthosis nigricans in childhood obesity. J Paediatr Child Health 2008; 44: 338-341.
12. Type 2 diabetes in children and adolescents. American Diabetes Association. Diabetes Care 2000; 23: 381-389.
13. Schwartz RA: Acanthosis nigricans. J Am Acad Dermatol 1994; 31: 1-19.
14. Fleming MG, Simon SI: Cutaneous insulin reaction resembling acanthosis nigricans. Arch Dermatol 1986; 122: 1054-1056.
15. Skouby SO: Update on the metabolic effects of oral contraceptives. J Obstet Gynaecol (Lahore) 1986; 6(suppl 2):S104-S109.
16. Stuart CA, Gilkison CR, Smith MM, Bosma AM, Keenan BS, Nagamani M: Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus. Clin Pediatr (Phila) 1998; 37: 73-79.
17. Matsuoka LY, Wortsman J, Gavin JR, Goldman J: Spectrum of endocrine abnormalities associated with acanthosis nigricans. Am J Med 1987; 83: 719-725.
18. Mellor-Pita S, Yebra-Bango M, Alfaro-Martinez J, Suárez E: Acanthosis nigricans: a new manifestation of insulin resistance in patients receiving treatment with protease inhibitors. Clin Infect Dis 2002; 34: 716-717.
19. Stals H, Vercammen C, Peeters C, Morren MA: Acanthosis nigricans caused by nicotinic acid: case report and review of the literature. Dermatology 1994; 189: 203-206.
20. Alatzoglou KS, Hindmarsh PC, Brain C, Torpiano J, Dattani MT: Acanthosis nigricans and insulin sensitivity in patients with achondroplasia and hypochodroplasia due to FGFR3 mutations. J Clin Endocrinol Metab 2009; 94: 3959-3963.
21. Kanazawa H, Tanaka H, Inoue M, Yamanaka Y, Namba N, Seino Y: Efficacy of growth hormone therapy for patients with skeletal dysplasia. J Bone Miner Metab 2003; 21: 307-310.
22. Hagenas L, Hertel T: Skeletal dysplasia, growth hormone treatment and body proportion: comparison with other syndromic and non-syndromic short children. Horm Res 2003; 60(suppl 3):65-70.
23. Billerey C, Chopin D, Aubriot-Lorton MH, Ricol D, Gil Diez de Medina S, Van Rhijn B, Bralet MP, Lefrere-Belda MA, Lahaye JB, Abbou CC, Bonaventure J, Zafrani ES, van der Kwast T, Thiery JP, Radvanyi F: Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol 2001; 158: 1955-1959.
24. Sibley K, Cuthbert-Heavens D, Knowles MA: Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma. Oncogene 2001; 20: 686-691.
25. Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP, Radvanyi F: Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 1999; 23: 18-20.
26. Wu R, Connolly D, Ngelangel C, Bosch FX, Muñoz N, Cho KR: Somatic mutations of fibroblast growth factor receptor 3 (FGFR3) are uncommon in carcinomas of the uterine cervix. Oncogene 2000; 19: 5543-5546.
27. Yee CJ, Lin O, Boyd J: Analysis of fibroblast growth factor receptor 3 S249C mutation in cervical carcinoma. J Natl Cancer Inst 2000; 92: 1848-1849.
28. Sibley K, Stern P, Knowles MA: Frequency of fibroblast growth factor receptor 3 mutations in sporadic tumours. Oncogene 2001; 20: 4416-4418.
29. Jang JH, Shin KH, Park JG: Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers. Cancer Res 2001; 61: 3541-3543.
30. Hernandez S, de Muga S, Agell L, Juanpere N, Esgueva R, Lorente JA, Mojal S, Serrano S, Lloreta J: FGFR3 mutations in prostate cancer: association with low-grade tumors. Mod Pathol 2009; 22: 848-856.
31. Chesi M, Nardini E, Brents LA, Schrock E, Ried T, Kuehl WM, Bergsagel PL: Frequent translocation t(4; 14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat Genet 1997; 16: 260-264.
32. L'Hote CG, Knowles MA: Cell responses to FGFR3 signalling: growth, differentiation and apoptosis. Exp Cell Res 2005; 304: 417-431.
33. van Rhijn BW, van Tilborg AA, Lurkin I, Bonaventure J, de Vries A, Thiery JP, van der Kwast TH, Zwarthoff EC, Radvanyi F: Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. Eur J Hum Genet 2002; 10: 819-824.
34. Zhang Y, Hiraishi Y, Wang H, Sumi KS, Hayashido Y, Toratani S, Kan M, Sato JD, Okamoto T: Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas. Int J Cancer 2005; 117: 166-168.
35. Hafner C, van Oers JM, Hartmann A, Landthaler M, Stoehr R, Blaszyk H, Hofstaedter F, Zwarthoff EC, Vogt T: High frequency of FGFR3 mutations in adenoid seborrheic keratoses. J Invest Dermatol 2006; 126: 2404-2407.
36. Hafner C, Hartmann A, Real FX, Hofstaedter F, Landthaler M, Vogt T: Spectrum of FGFR3 mutations in multiple intraindividual seborrheic keratoses. J Invest Dermatol 2007; 127: 1883-1885.
37. Hafner C, Lopez-Knowles E, Luis NM, Toll A, Baselga E, Fernandez-Casado A, Hernandez S, Ribe A, Mentzel T, Stoehr R, Hofstaedter F, Landthaler M, Vogt T, Pujol RM, Hartmann A, Real FX: Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proc Natl Acad Sci USA 2007; 104: 13450-13454.
38. Hida Y, Kubo Y, Arase S: Activation of fibroblast growth factor receptor 3 and oncogeneinduced senescence in skin tumours. Br J Dermatol 2009; 160: 1258-1263.
39. Hafner C, Hartmann A, van Oers JM, Stoehr R, Zwarthoff EC, Hofstaedter F, Landthaler M, Vogt T: FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization. Mod Pathol 2007; 20: 895-903.
40. Perez-Oliva N, Toribio J, Quinones PA: Histologic aspects of seborrheic keratosis (in Spanish). Med Cutan Ibero Lat Am 1990; 18: 70-77.
41. Hafner C, Vogt T, Landthaler M, Musebeck J: Somatic FGFR3 and PIK3CA mutations are present in familial seborrhoeic keratoses. Br J Dermatol 2008; 159: 214-217.
42. Hafner C, Stoehr R, van Oers JM, Zwarthoff EC, Hofstaedter F, Landthaler M, Hartmann A, Vogt T: FGFR3 and PIK3CA mutations are involved in the molecular pathogenesis of solar lentigo. Br J Dermatol 2009; 160: 546-551.
43. Mandinova A, Kolev V, Neel V, Hu B, Stonely W, Lieb J, Wu X, Colli C, Han R, Pazin M, Ostano P, Dummer R, Brissette JL, Dotto GP: A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans. J Clin Invest 2009; 119: 3127-3137.
44. Hafner C, van Oers JM, Vogt T, Landthaler M, Stoehr R, Blaszyk H, Hofstaedter F, Zwarthoff EC, Hartmann A: Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. J Clin Invest 2006; 116: 2201-2207.
45. Hernandez S, Toll A, Baselga E, Ribe A, Azua-Romeo J, Pujol RM, Real FX: Fibroblast growth factor receptor 3 mutations in epidermal nevi and associated low grade bladder tumors. J Invest Dermatol 2007; 127: 1664-1666.
46. García-Vargas A, Hafner C, Pérez-Rodríguez AG, Rodríguez-Rojas LX, González- Esqueda P, Stoehr R, Hernández-Torres M, Happle R: An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation. Am J Med Genet A 2008; 146A:2275-2279.
47. Collin B, Taylor IB, Wilkie AO, Moss C: Fibroblast growth factor receptor 3 (FGFR3) mutation in a verrucous epidermal naevus associated with mild facial dysmorphism. Br J Dermatol 2007; 156: 1353-1356.
48. Hafner C, Vogt T, Hartmann A: FGFR3 mutations in benign skin tumors. Cell Cycle 2006; 5: 2723-2728.
49. Ackerman AB, Ragaz A: The Lives of Lesions. New York, Masson, 1984.
50. Hafner C, Landthaler M, Mentzel T, Vogt T: FGFR3 and PIK3CA mutations in stucco keratosis and dermatosis papulosa nigra. Br J Dermatol 2010; 162: 508-512.
51. 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: No evidence of somatic FGFR3 mutation in various types of carcinoma. Oncogene 2001; 20: 5059-5061.
52. Chou A, Dekker N, Jordan RC: Identification of novel fibroblast growth factor receptor 3 gene mutations in actinic cheilitis and squamous cell carcinoma of the lip. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: 535-541.
53. Hafner C, Stoehr R, van Oers JM, Zwarthoff EC, Hofstaedter F, Klein C, Landthaler M, Hartmann A, Vogt T: The absence of BRAF, FGFR3, and PIK3CA mutations differentiates lentigo simplex from melanocytic nevus and solar lentigo. J Invest Dermatol 2009; 129: 2730-2735.
54. Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A, Emery C, Greulich H, Shah K, Sasaki H, Gazdar A, Minna J, Armstrong SA, Mellinghoff IK, Hodi FS, Dranoff G, Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K, Rubin MA, Moch H, Loda M, Catalona W, Fletcher J, Signoretti S, Kaye F, Anderson KC, Demetri GD, Dummer R, Wagner S, Herlyn M, Sellers WR, Meyerson M, Garraway LA: High-throughput oncogene mutation profiling in human cancer. Nat Genet 2007; 39: 347-351. (Pubitemid 46328493)