Bone tumors: an overview

Identity

Note

Primary skeletal neoplasms account for 0,2% of human tumors, whereas involvement of skeletal tissue by metastatic disease is much more common. Their soft tissue-related counterparts outnumber bone tumors by a margin of approximately 10:1. Because of their rarity, not much is known about the etiology and risk factors of bone tumors, although a difference in ethnical distribution has been observed. Bone tumors are mostly of mesenchymal origin, though for example Ewing sarcoma is thought to have neuroectodermal precursor cells. Classification of the World Health Organization will be followed in this overview. Grading of bone tumors is roughly based on the cellularity of the lesion compared to the amount of extracellulair matrix, nuclear features, the presence of mitotic figures and necrosis. Staging via the TNM system is normally not used, because metastases in lymph nodes are not frequent in these lesions. Therefore staging is based on degree of differentiation of the tumor tissue and local and distant spread of the tumor. Genetic information and references are provided for tumors investigated in more than a single case.

Classification

Cartilage tumors Osteochondroma Chondromas Enchondroma Periosteal chondroma Chondroblastoma Chondromyxoid fibroma Chondrosarcoma Dedifferentiated Mesenchymal Clear cell Periosteal Osteogenic tumors Osteoid osteoma Osteoblastoma Osteosarcoma Conventional Teleangiectatic Small cell Low grade central Secondary Parosteal Periosteal High grade surface Fibrogenic tumors Desmoplastic fibroma of bone Fibrosarcoma of bone Fibrohistiocytic tumors Histiocytoma of bone Ewing sarcoma/Primitive neuroectodermal tumor Giant cell tumors Giant cell tumor Notochordal tumors Chordoma Vascular tumors Haemangioma and related lesions Angiosarcoma Myogenic, lipogenic, neural and epithelial tumors Leiomyosarcoma of bone Lipoma of bone Adamantinoma and osteofibrous dysplasia Tumors of undefined neoplastic nature Aneurysmal bone cyst Simple bone cyst Fibrous dysplasia Langerhans cell histiocytosis (LCH)

Clinics and Pathology

Cytogenetics

Cartilage tumors Osteochondroma Germ line mutations in the tumorsupressor genes Exostosin-1 (EXT-1) located at 8q24 and Exostosin-2 (EXT-2) located at 11p11-p12 have been found in hereditary multiple osteochondromas (MO). Somatic mutations are extremely rare in these tumors. In four tumors aberrations involving the region 1p13-p22 were shown. Chondromas Enchondroma By conventional cytogenetic analysis, abnormalities involving chromosome 6 and the long arm of chromosome 12 have been detected. Periosteal chondroma This subtype has not been individually investigated. Chondroblastoma Although a dozen of case reports have been published, no specific alterations were found in these rare benign tumors. Chondromyxoid fibroma Structural rearrangements of chromosome 6 are found to be non-random, particularly involving the long arm (q13 and q25) and p25 on the short arm. Chondrosarcoma In most genetic studies no difference is made between peripheral, central chondrosarcoma and other subtypes. CGH revealed extensive genetic aberrations; gains of whole chromosomes or chromosome arms at 20q (32-38%), 20p (24-31%), and 14q23-qter (24-28%). In a comparative study, 19 of 20 peripheral chondrosarcoma showed LOH at the loci for EXT, EXTL, 13q14, 17p14, 17p13, 9p21 and chromosome 10, while only 3 of 12 central chondrosarcoma did. In addition the ploidy status in peripheral chondrosarcoma showed wide variation (0,56-2,01), whereas central chondrosarcomas were predominantly periploid. Dedifferentiated In the cartilaginous, as well as in the dedifferentiated part of the tumor an identical somatic 6 bp deletion in exon 7 of p53 and loss of the same copy on chromosome 13 had been found. These findings provide evidence for a common origin of both parts. Mesenchymal A Robertsonian (13;21) translocation, der(13;21)(q10;q10), was detected in two cases, together with loss of material from chromosome 8 and 20 and gain of material from chromosome 8. Clear cell No specific alterations have been reported. Periosteal No specific alterations have been reported.

Cytogenetics

Osteogenic tumors Osteoid osteoma Involvement of band 22q13 and loss of the distal part of arm 17q were detected in two out of three analyzed cases. Osteoblastoma No consistent aberrations have been detected in four cases, although clues are leading to deregulation of the cell cycle. No telomerase activity could be found. Osteosarcoma Conventional Although most osteosarcomas reveal complex chromosomal aberrations, no specific alterations have been found. Amplification at 1q21-23 and 17p, together with co-amplification of 12q13-15 are frequently reported. In 14-27% of osteosarcomas, the MDM2 gene is amplified and in 41% the PRIM1 gene. Amplification of the CDK4 gene is found in aggressive lesions. Chromosome 12p is differently amplified in low- versus high-grade osteosarcomas. The MYC gene has been shown to be amplified in 44% of osteosarcoma (8q24). Teleangiectatic In contrast to the conventional osteosarcomas, no amplifications were detected in four cases. Complex chromosomal changes were found. Small cell No genetic alterations have been reported on this subtype of osteosarcoma. Low grade central The complex aberrations found in high-grade osteosarcomas could not be identified in these low-grade variants. Recurrent gains have been reported with minimal common regions at 12q13-14, 12p and 6p21. Secondary In tumors developing in bone after radiation, chromosomal losses are more frequently observed than gains. Especially 1p, which is lost in 3% of the conventional type, is lost in 57% of the radiation-associated type. In osteosarcomas secondary to Paget Disease of Bone (PDB) LOH is found at 18q, the locus for PDB. Parosteal Ring chromosomes are reported as the sole alteration in parosteal osteosarcoma. Using FISH techniques, the SAS, CDK4 and MDM2 genes are shown to be co-amplified with a minimal common region at 12q13-15 in the ring chromosomes. Periosteal Complex chromosomal aberrations were reported. High grade surface These lesions have not been studied as a specific subtype.

Cytogenetics

Fibrogenic tumors Desmoplastic fibroma of bone Like in desmoid tumors, trisomies 8 and 20 are commonly found. Fibrosarcoma of bone No cytogenetic investigations on fibrosarcoma have been published.

Cytogenetics

Fibrohistiocytic tumors Histiocytoma of bone Of the benign form of this tumor, no cytogenetic information is available. Its malignant counterpart shows LOH at chromosome 9p21-22, which has also been shown by CGH before.

Cytogenetics

Ewing sarcoma/Primitive neuroectodermal tumor The most common rearrangement (85%) in this tumor is translocation t(11;22)(q24;q12). Consequently, this leads to the fusion protein EWS/FLI1. Other translocations found in the Ewing Sarcoma gene are listed below: fusion of to translocation % EWS FLI1 t(11;22)(q24;q12) 85 EWS ERG t(21;22)(q22;q12) 10-15 EWS ETV1 t(7;22)(p22;q12) < 1 EWS FEV t(2;22)(q36;q12) < 1 EWS E1AF t(17;22)(q21;q12) < 1

Cytogenetics

Giant cell tumors Giant cell tumor Reduction in length of the telomeres, as well as telomeric association, has been demonstrated in these tumors. Most commonly 11p, 13p, 14p, 15p, 19q, 20q and 21p are affected.

Cytogenetics

Notochordal tumors Chordoma Nine of sixteen investigated chordomas were hypodiploid with a chromosome number ranging from 33 to 44. Chromosomes 3, 4, 10, and 13 are most commonly lost, and in half of the cases the following segments are lost up to the telomere: 1p31, 3p21, 3q21, 9p24, 17q11. Because LOH is found at band 1p36, a tumor suppressor gene is thought to exist on distal 1p.

Cytogenetics

Vascular tumors Haemangioma and related lesions No cytogenetic investigations reported. Angiosarcoma An identical translocation of chromosomes 1 and 3 has been reported in two epithelioid haemangioendotheliomas.

Cytogenetics

Myogenic, lipogenic, neural and epithelial tumors Leiomyosarcoma of bone 5 Grade IIB tumors demonstrated a rate of genomic loss of 90%, whereas high micro satellite instability was not observed. Allelotyping revealed loss of pRb in the tumors. In addition, chromosomal loss was noticed in human telomerase subunit-linked markers. Lipoma of bone Only one case study is published about the benign form of this tumor. On its malignant counterpart, liposarcoma of bone, no genetic information has been published. Adamantinoma and osteofibrous dysplasia Cumulating evidence indicates that classic adamantinomas derive from their osteofibrous dysplasia (OFD)-like counterparts. OFD and adamantinoma show common cytogenetic abnormalities. In 15 cases of adamantinoma (n=11) and OFD (n=4) trisomies of chromosomes 7, 8, 12, 19 and 21 were detected. These findings further substantiate the clonal origin of OFD and the common histogenesis of OFD and adamantinoma.

Cytogenetics

Tumors of undefined neoplastic nature Aneurysmal bone cyst Aneurysmal bone cysts can be primary or secondary to other bone lesions. Chromosome bands 16q22 and/or 17p13 (USP6 gene) are non-randomly rearranged in ABC, regardless of tumor type (classic and solid) and of location (osseous and extraosseous). However, rearrangements are absent in secondary ABC. A recurrent t(16;17)(q22;p13) has been identified, but other chromosomal segments as translocation partner for each chromosome have been described. Simple bone cyst Only one case report describes structural rearrangements. Fibrous dysplasia Two fibrous dysplasia cases exhibited either a completely normal karyotype or single cell aberrations. Evidence that this lesion is neoplastic comes from the fact that clonal chromosomal aberrations have been found. In monostotic as well as polyostotic lesions activating GNAS1(20q13.2) mutations, known from the McCune-Albright syndrome, have been demonstrated. Langerhans cell histiocytosis (LCH) Studies of X-chromosome inactivation demonstrated that LCH is clonal.

Cytogenetics

Congenital and inherited syndromes Beckwith-Wiedemann syndrome This syndrome, which is caused by heterogenic genetic changes on 11q15, is subject to genomic imprinting. 3 Beckwith-Wiedemann syndrome chromosome regions (BWSCR) have been identified: BWSC1 near INS/IGF2, BWSC2 5 Mb proximal to BWSC1, and BWSC3 2 Mb even more proximal. Enchondromatosis: Ollier disease and Maffucci syndrome These syndromes are non-hereditary although a case of familial clustering has been reported. Mutations in the PTH receptor 1 have been found in two cases, but these results could not be confirmed in a larger series of 31 patients, suggesting that PTHR1 is not the culprit for enchondromatosis. McCune-Albright syndrome Mutations in the GNAS1 gene, located on 20q13, change the structure of the G-protein a-stimulatory subunit. Dysfunctions of the heterotrimeric G-protein complexes lead to this non-familial occurring disorder. Multiple osteochondromatosis(MO)/Hereditary Multiple Exostosis Mutations in one of the two exostosin (EXT) genes are responsible for this autosomal dominant syndrome. EXT1 is located at 8q24 and EXT2 at 11p11-p12. Most mutations are either nonsense, frame shift or splice-site mutations, leading to premature termination of the EXT proteins. This causes alteration of the gene products, which are functioning in the endoplasmatic reticulum as transmembrane glycoproteins, and will affect the biosynthesis of heparan sulphate proteoglycans, leading to altered growth factor signaling. Familial Paget Disease of Bone Familial Paget Disease of Bone (PDB) demonstrates linkage to chromosome 18q. Some cases (PDB type 2) are caused by mutations in the TNFRSF11A gene on chromosome 18q22.1, which encodes RANK, a protein essential in osteoclast formation. The phenotype linked to chromosome 5q35 (PDB type 3) is caused by mutations in the SQSTM1 gene, the product of which is associated with the RANK pathway.

Bibliography

Telomeric associations and consistent growth factor overexpression detected in giant cell tumor of bone.

Schwartz HS, Butler MG, Jenkins RB, Miller DA, Moses HL

Cancer genetics and cytogenetics. 1991 ; 56 (2) : 263-276.

PMID 1756472

Clonal karyotypic aberrations in enchondromas.

Bridge JA, Persons DL, Neff JR, Bhatia P

Cancer detection and prevention. 1992 ; 16 (4) : 215-219.

PMID 1458512

Biologic and clinical significance of cytogenetic and molecular cytogenetic abnormalities in benign and malignant cartilaginous lesions.

Bridge JA, Bhatia PS, Anderson JR, Neff JR

Cancer genetics and cytogenetics. 1993 ; 69 (2) : 79-90.

PMID 8402563

Rearrangement of band q13 on both chromosomes 12 in a periosteal chondroma.

Mandahl N, WillˆŠn H, Rydholm A, Heim S, Mitelman F

Genes, chromosomes & cancer. 1993 ; 6 (2) : 121-123.

PMID 7680888

Clonal chromosomal abnormalities in osteofibrous dysplasia. Implications for histopathogenesis and its relationship with adamantinoma.

Bridge JA, Dembinski A, DeBoer J, Travis J, Neff JR

Cancer. 1994 ; 73 (6) : 1746-1752.

PMID 8156503

Langerhans'-cell histiocytosis (histiocytosis X)--a clonal proliferative disease.

Willman CL, Busque L, Griffith BB, Favara BE, McClain KL, Duncan MH, Gilliland DG

The New England journal of medicine. 1994 ; 331 (3) : 154-160.

PMID 8008029

Mesenchymal chondrosarcoma. A cytogenetic, immunohistochemical and ultrastructural study.

Dobin SM, Donner LR, Speights VO Jr

Cancer genetics and cytogenetics. 1995 ; 83 (1) : 56-60.

PMID 7656206

DNA aberrations in the epithelial cell component of adamantinoma of long bones.

Hazelbag HM, Fleuren GJ, Cornelisse CJ, van den Broek LJ, Taminiau AH, Hogendoorn PC

The American journal of pathology. 1995 ; 147 (6) : 1770-1779.

PMID 7495301

Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization.

Tarkkanen M, Karhu R, Kallioniemi A, Elomaa I, Kivioja AH, Nevalainen J, Bˆhling T, Karaharju E, Hyytinen E, Knuutila S

Cancer research. 1995 ; 55 (6) : 1334-1338.

PMID 7882332

Positional cloning of a gene involved in hereditary multiple exostoses.

Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul EV, De Boulle K, de Vries BB, Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet L, van den Ouweland AM, McGaughran J, Halley DJ, Willems PJ

Human molecular genetics. 1996 ; 5 (10) : 1547-1557.

PMID 8894688

Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature.

Bridge JA, Nelson M, McComb E, McGuire MH, Rosenthal H, Vergara G, Maale GE, Spanier S, Neff JR

Cancer genetics and cytogenetics. 1997 ; 95 (1) : 74-87.

PMID 9140456

The pericentromeric inversion, inv (6)(p25q13), is a novel diagnostic marker in chondromyxoid fibroma.

Granter SR, Renshaw AA, Kozakewich HP, Fletcher JA

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 1998 ; 11 (11) : 1071-1074.

PMID 9831204

Cytogenetic analysis of a scapular chondromyxoid fibroma.

Halbert AR, Harrison WR, Hicks MJ, Davino N, Cooley LD

Cancer genetics and cytogenetics. 1998 ; 104 (1) : 52-56.

PMID 9648559

Evidence of an association between 6q13-21 chromosome aberrations and locally aggressive behavior in patients with cartilage tumors.

Sawyer JR, Swanson CM, Lukacs JL, Nicholas RW, North PE, Thomas JR

Cancer. 1998 ; 82 (3) : 474-483.

PMID 9452264

Significance of abnormalities of chromosomes 5 and 8 in chondroblastoma.

Swarts SJ, Neff JR, Johansson SL, Nelson M, Bridge JA

Clinical orthopaedics and related research. 1998 : 189-193.

PMID 9584382

EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas.

BovˆŠe JV, Cleton-Jansen AM, Wuyts W, Caethoven G, Taminiau AH, Bakker E, Van Hul W, Cornelisse CJ, Hogendoorn PC

American journal of human genetics. 1999 ; 65 (3) : 689-698.

PMID 10441575

Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma.

BovˆŠe JV, Cleton-Jansen AM, Kuipers-Dijkshoorn NJ, van den Broek LJ, Taminiau AH, Cornelisse CJ, Hogendoorn PC

Genes, chromosomes & cancer. 1999 ; 26 (3) : 237-246.

PMID 10502322

Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis.

BovˆŠe JV, Cleton-Jansen AM, Rosenberg C, Taminiau AH, Cornelisse CJ, Hogendoorn PC

The Journal of pathology. 1999 ; 189 (4) : 454-462.

PMID 10629543

Recurrent chromosome aberrations in fibrous dysplasia of the bone: a report of the CHAMP study group. CHromosomes And MorPhology.

Dal Cin P, Sciot R, Brys P, De Wever I, Dorfman H, Fletcher CD, Jonsson K, Mandahl N, Mertens F, Mitelman F, Rosai J, Rydholm A, Samson I, Tallini G, Van den Berghe H, Vanni R, Willen H

Cancer genetics and cytogenetics. 2000 ; 122 (1) : 30-32.

PMID 11104029

Clonal chromosome abnormalities in enchondromas and chondrosarcomas.

Gunawan B, Weber M, Bergmann F, Wildberger J, Niethard FU, Fˆşzesi L

Cancer genetics and cytogenetics. 2000 ; 120 (2) : 127-130.

PMID 10942802

Molecular Cytogenetics in Ewing Tumors: Diagnostic and Prognostic Information.

Hattinger CM, Zoubek A, Ambros PF

Onkologie. 2000 ; 23 (5) : 416-422.

PMID 11441235

Malignant fibrous histiocytoma: inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22-evidence for a common genetic defect.

Martignetti JA, Gelb BD, Pierce H, Picci P, Desnick RJ

Genes, chromosomes & cancer. 2000 ; 27 (2) : 191-195.

PMID 10612808

Recurrent anomalies of 6q25 in chondromyxoid fibroma.

Safar A, Nelson M, Neff JR, Maale GE, Bayani J, Squire J, Bridge JA

Human pathology. 2000 ; 31 (3) : 306-311.

PMID 10746672

Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma.

Simons A, Schepens M, Jeuken J, Sprenger S, van de Zande G, Bjerkehagen B, Forus A, Weibolt V, Molenaar I, van den Berg E, Myklebost O, Bridge J, van Kessel AG, Suijkerbuijk R

Cancer genetics and cytogenetics. 2000 ; 118 (2) : 89-98.

PMID 10748288

EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis.

Stickens D, Brown D, Evans GA

Developmental dynamics : an official publication of the American Association of Anatomists. 2000 ; 218 (3) : 452-464.

PMID 10878610

Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma.

Tsuchiya T, Sekine K, Hinohara S, Namiki T, Nobori T, Kaneko Y

Cancer genetics and cytogenetics. 2000 ; 120 (2) : 91-98.

PMID 10942797

Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes.

BovˆŠe JV, Sciot R, Cin PD, Debiec-Rychter M, van Zelderen-Bhola SL, Cornelisse CJ, Hogendoorn PC

Diagnostic molecular pathology : the American journal of surgical pathology, part B. 2001 ; 10 (4) : 228-235.

PMID 11763313

Genome-wide analysis of sixteen chordomas by comparative genomic hybridization and cytogenetics of the first human chordoma cell line, U-CH1.

Scheil S, Brˆşderlein S, Liehr T, Starke H, Herms J, Schulte M, Mˆller P

Genes, chromosomes & cancer. 2001 ; 32 (3) : 203-211.

PMID 11579460

Cytogenetic and molecular cytogenetic evidence of recurrent 8q24.1 loss in osteochondroma.

Feely MG, Boehm AK, Bridge RS, Krallman PA, Neff JR, Nelson M, Bridge JA

Cancer genetics and cytogenetics. 2002 ; 137 (2) : 102-107.

PMID 12393280

WHO Classification of tumours. Pathology & Genetics. Tumours of Bone and Soft tissue.

Fletcher CDM, Unni KK, and Mertens F

IARC Press. : page L.

Translocation der(13;21)(q10;q10) in skeletal and extraskeletal mesenchymal chondrosarcoma.

Naumann S, Krallman PA, Unni KK, Fidler ME, Neff JR, Bridge JA

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2002 ; 15 (5) : 572-576.

PMID 12011263

Recurring breakpoints of 1p13 approximately p22 in osteochondroma.

Sawyer JR, Thomas EL, Lukacs JL, Swanson CM, Ding Y, Parham DM, Thomas JR, Nicholas RW

Cancer genetics and cytogenetics. 2002 ; 138 (2) : 102-106.

PMID 12505252

Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group.

Tallini G, Dorfman H, Brys P, Dal Cin P, De Wever I, Fletcher CD, Jonson K, Mandahl N, Mertens F, Mitelman F, Rosai J, Rydholm A, Samson I, Sciot R, Van den Berghe H, Vanni R, WillˆŠn H

The Journal of pathology. 2002 ; 196 (2) : 194-203.

PMID 11793371

Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma.

Rˆpke M, Boltze C, Neumann HW, Roessner A, Schneider-Stock R

Pathology, research and practice. 2003 ; 199 (6) : 437-444.

PMID 12924447

Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: chondrosarcoma and other cartilaginous neoplasms.

Sandberg AA, Bridge JA

Cancer genetics and cytogenetics. 2003 ; 143 (1) : 1-31.

PMID 12742153

Multiple Osteochondromas: Clinicopathological and Genetic Spectrum and Suggestions for Clinical Management.

Hameetman L, BovˆÉŹŠe JVMG, Taminiau AHM, Kroon HM, and Hogendoorn PCW

Hereditary Cancer in Clinical Practice. 2004 ; 2 : 161-173.

USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts.

Oliveira AM, Perez-Atayde AR, Inwards CY, Medeiros F, Derr V, Hsi BL, Gebhardt MC, Rosenberg AE, Fletcher JA

The American journal of pathology. 2004 ; 165 (5) : 1773-1780.

PMID 15509545

Cytogenetic distinction among benign fibro-osseous lesions of bone in children and adolescents: value of karyotypic findings in differential diagnosis.

Parham DM, Bridge JA, Lukacs JL, Ding Y, Tryka AF, Sawyer JR

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2004 ; 7 (2) : 148-158.

PMID 15022060

Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C.

Rozeman LB, Sangiorgi L, Briaire-de Bruijn IH, Mainil-Varlet P, Bertoni F, Cleton-Jansen AM, Hogendoorn PC, BovˆŠe JV

Human mutation. 2004 ; 24 (6) : 466-473.

PMID 15523647

Genetic instability in primary leiomyosarcoma of bone.

Verelst SJ, Hans J, Hanselmann RG, Wirbel RJ

Human pathology. 2004 ; 35 (11) : 1404-1412.

PMID 15668899

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Contributor(s)

Written	03-2005	Yvonne M Schrage, Judith VMG Bovée

Citation

This paper should be referenced as such :

Schrage YM, Bovée JVMG . Bone tumors: an overview. Atlas Genet Cytogenet Oncol Haematol. March 2005 . URL : http://AtlasGeneticsOncology.org/Genes/BoneTumorID5143.html

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