SH3BP2 Is Rarely Mutated in Exon 9 in Giant Cell Lesions Outside Cherubism

Giant cell tumor of bone and giant cell reparative granuloma are benign lesions with prominent giant (multinucleated) cells, and an understanding of the molecular biology and genetics of these lesions will likely aid in more effective treatment. Cherubism is a benign lesion of the maxilla and mandible histologically similar to giant cell tumor of bone and giant cell reparative granuloma. Germline mutations in exon 9 of the gene encoding Src homology 3 binding protein 2 (SH3BP2) occur in most patients with cherubism. We therefore hypothesized SH3BP2 and its putative downstream effector nuclear factor of activated T cells c1 isoform (NFATc1) are highly expressed in sporadic nonsyndromic giant cell lesions and associated with somatic SH3BP2 mutations. We analyzed giant cell lesions for SH3BP2 and NFATc1 expression by RNA blot and/or immunohistochemistry and for exon 9 SH3BP2 mutations. We found the SH3BP2 transcripts and protein were abundantly expressed in giant cell tumors of bone, as well as NFATc1 protein. Sequencing of exon 9 of SH3BP2 was normal in all sporadic nonsyndromic giant cell lesions. Although many multinucleated giant cell lesions of bone share histologic features, the primary genetic defect in cherubism and these other giant cell lesions appears different.

[1]  M. V. van Maarle,et al.  DNA analysis of the SH3BP2 gene in patients with aggressive central giant cell granuloma. , 2007, The British journal of oral & maxillofacial surgery.

[2]  R. Kohanski,et al.  Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation , 2006, Human mutation.

[3]  J. Bagan,et al.  Cherubism: a clinical, radiographic, and histopathologic comparison of 7 cases. , 2006, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[4]  Robert J. Marinelli,et al.  A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C. Ding,et al.  A highly sensitive polymerase chain reaction method detects activating mutations of the GNAS gene in peripheral blood cells in McCune-Albright syndrome or isolated fibrous dysplasia. , 2005, The Journal of bone and joint surgery. American volume.

[6]  E. Reichenberger,et al.  Noonan‐like syndrome mutations in PTPN11 in patients diagnosed with cherubism , 2005, Clinical genetics.

[7]  G. Yu,et al.  Clinicopathologic study of 24 cases of cherubism. , 2005, International journal of oral and maxillofacial surgery.

[8]  J. Lange,et al.  Clinical and radiological features of central giant-cell lesions of the jaw. , 2005, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[9]  Amnon Altman,et al.  The adaptor protein 3BP2 associates with VAV guanine nucleotide exchange factors to regulate NFAT activation by the B-cell antigen receptor. , 2005, Blood.

[10]  Hiroshi Takayanagi,et al.  Mechanistic insight into osteoclast differentiation in osteoimmunology , 2005, Journal of Molecular Medicine.

[11]  J. Woo,et al.  The Calcineurin/Nuclear Factor of Activated T Cells Signaling Pathway Regulates Osteoclastogenesis in RAW264.7 Cells* , 2004, Journal of Biological Chemistry.

[12]  Y. Matsubara,et al.  A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism. , 2003, The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association.

[13]  M. Ostrowski,et al.  Giant cell reparative granuloma of the orbit associated with cherubism. , 2003, Ophthalmology.

[14]  Alain Bernard,et al.  The Chaperone Protein 14-3-3 Interacts with 3BP2/SH3BP2 and Regulates Its Adapter Function* , 2003, The Journal of Biological Chemistry.

[15]  B. Hoffmeister,et al.  Klinische und molekulargenetische Befunde bei Familien mit Cherubismus über 3 Generationen , 2003, Mund-, Kiefer- und Gesichtschirurgie.

[16]  Hiroshi Takayanagi,et al.  Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. , 2002, Developmental cell.

[17]  K. Sada,et al.  Regulation of FcεRI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells , 2002 .

[18]  Bruce D Gelb,et al.  PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. , 2002, American journal of human genetics.

[19]  J. Eskew,et al.  Clonality studies in giant cell tumor of bone , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[20]  M. Earley,et al.  Cherubism and its charlatans. , 2001, British journal of plastic surgery.

[21]  F. Gannon,et al.  From the archives of AFIP. Imaging of giant cell tumor and giant cell reparative granuloma of bone: radiologic-pathologic correlation. , 2001, Radiographics : a review publication of the Radiological Society of North America, Inc.

[22]  M. Habal,et al.  Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism , 2001, Nature Genetics.

[23]  A. Sigurdsson,et al.  The gene for cherubism maps to chromosome 4p16.3. , 1999, American journal of human genetics.

[24]  A. Battaglia,et al.  Health supervision and anticipatory guidance of individuals with Wolf-Hirschhorn syndrome. , 1999, American journal of medical genetics.

[25]  J. Hernandez,et al.  Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation. , 1998, Immunity.

[26]  T. Pawson,et al.  Signaling through scaffold, anchoring, and adaptor proteins. , 1997, Science.

[27]  R. Myers,et al.  Identification and characterization of the human homologue of SH3BP2, an SH3 binding domain protein within a common region of deletion at 4p16.3 involved in bladder cancer. , 1997, Genomics.

[28]  C. Gilks,et al.  Giant cell tumor of tendon sheath is a polyclonal cellular proliferation. , 1997, Human pathology.

[29]  P. Chomczyński,et al.  One-hour downward capillary blotting of RNA at neutral pH. , 1994, Analytical biochemistry.

[30]  P Cicchetti,et al.  Identification of a ten-amino acid proline-rich SH3 binding site. , 1993, Science.

[31]  G. Kaugars,et al.  Cherubism: diagnosis, treatment, and comparison with central giant cell granulomas and giant cell tumors. , 1992, Oral surgery, oral medicine, and oral pathology.

[32]  L. Villa-komaroff,et al.  Optimizing the northern blot procedure. , 1990, BioTechniques.

[33]  M. Mahmoudi,et al.  Comparison of two different hybridization systems in northern transfer analysis. , 1989, BioTechniques.

[34]  D A Goldberg,et al.  Isolation and partial characterization of the Drosophila alcohol dehydrogenase gene. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[35]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[36]  H. Boedtker,et al.  RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. , 1977, Biochemistry.

[37]  H. Yoshida,et al.  Giant cell tumor of bone , 2004, Virchows Archiv A.

[38]  H. Peters,et al.  [Clinical and molecular genetic observations on families with cherubism over three generations]. , 2003, Mund-, Kiefer- und Gesichtschirurgie : MKG.

[39]  K. Sada,et al.  Regulation of FcepsilonRI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells. , 2002, Blood.

[40]  F. Salzano,et al.  The gene for cherubism maps to chromosome 4p16. , 1999, American journal of human genetics.