Molecular pathology and its diagnostic use in bone tumors

Cancer Genetics

Volumn 205, Issue 5, 2012, Pages 193-204

  Szuhai, Karoly ^a   Cleton Jansen, Anne Marie ^a   Hogendoorn, Pancras C W ^a   Bovée, Judith V M G ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Bone tumor; Molecular diagnostics; Molecular pathology

Indexed keywords

ANEURYSMAL BONE CYST; BONE TUMOR; CHONDROSARCOMA; CHORDOMA; CHROMOSOME TRANSLOCATION; DIAGNOSTIC VALUE; EWING SARCOMA; FIBROUS DYSPLASIA; GENE AMPLIFICATION; GENE MUTATION; GENETIC STABILITY; HISTOLOGY; HUMAN; IMMUNOHISTOCHEMISTRY; KARYOTYPE; MOLECULAR DIAGNOSIS; MOLECULAR PATHOLOGY; OSTEOSARCOMA; PATHOLOGIST; PRIORITY JOURNAL; RADIODIAGNOSIS; RARE DISEASE; REVIEW; SARCOMA; TECHNOLOGY; CHROMOSOME ANALYSIS; COMPARATIVE GENOMIC HYBRIDIZATION; GENE TRANSLOCATION; GENETIC SCREENING; GENETICS; METHODOLOGY; MUTATION; PATHOLOGY;

BONE NEOPLASMS; COMPARATIVE GENOMIC HYBRIDIZATION; CYTOGENETIC ANALYSIS; GENE AMPLIFICATION; GENETIC TESTING; HUMANS; KARYOTYPE; MUTATION; TRANSLOCATION, GENETIC;

EID: 84865392209     PISSN: 22107762     EISSN: 22107770     Source Type: Journal    
DOI: 10.1016/j.cancergen.2012.04.001     Document Type: Review

References (99)

1. Tomlins S.A., Rhodes D.R., Perner S., et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005, 310:644-648.
2. Wang L., Motoi T., Khanin R., et al. Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes Chromosomes Cancer 2012, 51:127-139.
3. Errani C., Zhang L., Sung Y.S., et al. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer 2011, 50:644-653.
4. Mendlick M.R., Nelson M., Pickering D., et al. Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma. Am J Surg Pathol 2001, 25:684-687.
5. Tanas M.R., Sboner A., Oliveira A.M., et al. Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med 2011, 3. 98.
6. Walther C., Domanski H.A., von Steyern F.V., et al. Chromosome banding analysis of cells from fine-needle aspiration biopsy samples from soft tissue and bone tumors: is it clinically meaningful?. Cancer Genet 2011, 204:203-206.
7. Szuhai K., Tanke H. COBRA: combined binary ratio labeling of nucleic-acid probes for multi-color fluorescence in situ hybridization karyotyping. Nature Protocols 2006, 1:264-275.
8. Szuhai K., Jennes I., de Jong D., et al. Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients. Hum Mutat 2011, 32:2036-2049.
9. Jennes I., de Jong D., Mees K., et al. Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 Multiple Osteochondromas families. BMC Med Genet 2011, 12:85.
10. De Jong D., Verbeke S.L., Meijer D., et al. Opening the archives for state of the art tumour genetic research: sample processing for array-CGH using decalcified, formalin-fixed, paraffin-embedded tissue-derived DNA samples. BMC Res Notes 2011, 4:1.
11. Mohseny A.B., Tieken C., Van der Velden P.A., et al. Small deletions but not methylation underlie CDKN2A/p16 loss of expression in conventional osteosarcoma. Genes Chromosomes Cancer 2010, 49:1095-1103.
12. Savola S., Nardi F., Scotlandi K., et al. Microdeletions in 9p21.3 induce false negative results in CDKN2A FISH analysis of Ewing sarcoma. Cytogenet Genome Res 2007, 119:21-26.
13. Amary M.F., Bacsi K., Maggiani F., et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol 2011, 224:334-343.
14. Pansuriya T.C., van Eijk R., d'Adamo P., et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet 2011, 43:1256-1261.
15. van Eijk R., Licht J., Schrumpf M., et al. Rapid KRAS, EGFR, BRAF and PIK3CA mutation analysis of fine needle aspirates from non-small-cell lung cancer using allele-specific qPCR. PLoS ONE 2011, 6:e17791.
16. Setty P., Hammes J., Rothamel T., et al. A pyrosequencing-based assay for the rapid detection of IDH1 mutations in clinical samples. J Mol Diagn 2010, 12:750-756.
17. Cuppen E. Genotyping by Allele-Specific Amplification (KASPar). CSH Protoc 2007, 2007. db.
18. Sankar S., Lessnick S.L. Promiscuous partnerships in Ewing's sarcoma. Cancer Genet 2011, 204:351-365.
19. Alava Ed., Kawai A., Healy J.H., et al. EWS-FL11 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol 1998, 16:1248-1255.
20. van Doorninck J.A., Ji L., Schaub B., et al. Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol 2010, 28:1989-1994.
21. Le Deley M.C., Delattre O., Schaefer K.L., et al. Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. J Clin Oncol 2010, 28:1982-1988.
22. Graham C., Chilton-MacNeill S., Zielenska M., et al. The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas. Hum Pathol 2012, 43:180-189.
23. Italiano A., Sung Y.S., Zhang L., et al. High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas. Genes Chromosomes Cancer 2012, 51:207-218.
24. Szuhai K., Ijszenga M., de Jong D., et al. The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology. Clin Cancer Res 2009, 15:2259-2268.
25. Panoutsakopoulos G., Pandis N., Kyriazoglou I., et al. Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts. Genes Chromosomes Cancer 1999, 26:265-266.
26. Oliveira A.M., Hsi B.L., Weremowicz S., et al. USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer Res 2004, 64:1920-1923.
27. Oliveira A.M., Perez-Atayde A.R., Dal Cin P., et al. Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene 2005, 24:3419-3426.
28. Oliveira A.M., Chou M.M., Perez-Atayde A., et al. Aneurysmal bone cyst: a neoplasm driven by upregulation of the USP6 oncogene. J Clin Oncol 2006, 24:e1.
29. Masuda-Robens J.M., Kutney S.N., Qi H., et al. The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling. Mol Cell Biol 2003, 23:2151-2161.
30. Ye Y., Pringle L.M., Lau A.W., et al. TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene 2010, 29:3619-3629.
31. Lau A.W., Pringle L.M., Quick L., et al. TRE17/ubiquitin-specific protease 6 (USP6) oncogene translocated in aneurysmal bone cyst blocks osteoblastic maturation via an autocrine mechanism involving bone morphogenetic protein dysregulation. J Biol Chem 2010 Nov 19, 285(47):37111-37120.
32. Oliveira A.M., Perez-Atayde A.R., Inwards C.Y., et al. USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol 2004, 165:1773-1780.
33. Sukov W.R., Franco M.F., Erickson-Johnson M., et al. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of " myositis ossificans-like lesions" are the early phases in the formation of soft-tissue aneurysmal bone cyst. Skeletal Radiol 2008, 37:321-327.
34. Erickson-Johnson M.R., Chou M.M., Evers B.R., et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest 2011, 91:1427-1433.
35. Dal Cin P., Sciot R., Brys P., et al. Recurrent chromosome aberrations in fibrous dysplasia of the bone: a report of the CHAMP study group. CHromosomes And MorPhology. Cancer Genet Cytogenet 2000, 122:30-32.
36. Idowu B.D., Al-Adnani M., O'Donnell P., et al. A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone. Histopathology 2007, 50:691-704.
37. Bianco P., Riminucci M., Majolagbe A., et al. Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone. J Bone Miner Res 2000, 15:120-128.
38. Okamoto S., Hisaoka M., Ushijima M., et al. Activating Gs(alpha) mutation in intramuscular myxomas with and without fibrous dysplasia of bone. Virchows Arch 2000, 437:133-137.
39. Willems S.M., Mohseny A.B., Balog C., et al. Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix. J Cell Mol Med 2009, 7:1301.
40. Delaney D., Diss T.C., Presneau N., et al. GNAS1 mutations occur more commonly than previously thought in intramuscular myxoma. Mod Pathol 2009, 22:718-724.
41. Faivre L., Nivelon-Chevallier A., Kottler M.L., et al. Mazabraud syndrome in two patients: clinical overlap with McCune-Albright syndrome. Am J Med Genet 2001, 99:132-136.
42. Pollandt K., Engels C., Kaiser E., et al. Gsalpha gene mutations in monostotic fibrous dysplasia of bone and fibrous dysplasia-like low-grade central osteosarcoma. Virchows Arch 2001, 439:170-175.
43. Sakamoto A., Oda Y., Iwamoto Y., et al. A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to Gsalpha mutation at the Arg201 codon: polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues. J Mol Diagn 2000, 2:67-72.
44. Patel M.M., Wilkey J.F., Abdelsayed R., et al. Analysis of GNAS mutations in cemento-ossifying fibromas and cemento-osseous dysplasias of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010, 109:739-743.
45. Toyosawa S., Yuki M., Kishino M., Ogawa Y., et al. Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization. Mod Pathol 2007, 20:389-396.
46. Cartilage tumours. World health organization classification of tumours. Pathology and genetics. Tumours of soft tissue and bone 2002, 234-257. World Health Organization, World Health Organization, Geneva Switzerland. C.D.M. Fletcher, K.K. Unni, F. Mertens (Eds.).
47. Ahn J., Ludecke H.-J., Lindow S., et al. Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nature Genet 1995, 11:137-143.
48. Stickens D., Clines G., Burbee D., et al. The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nature Genet 1996, 14:25-32.
49. Wuyts W., Van Hul W., Wauters J., et al. Positional cloning of a gene involved in hereditary multiple exostoses. Hum Mol Genet 1996, 5:1547-1557.
50. Bernard M.A., Hall C.E., Hogue D.A., et al. Diminished levels of the putative tumor suppressor proteins EXT1 and EXT2 in exostosis chondrocytes. Cell Motil Cytoskeleton 2001, 48:149-162.
51. Bovee J.V.M.G., Cleton-Jansen A.M., Wuyts W., et al. EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas. Am J Hum Genet 1999, 65:689-698.
52. Hameetman L., Szuhai K., Yavas A., et al. The role of EXT1 in non hereditary osteochondroma: identification of homozygous deletions. J Natl Cancer Inst 2007, 99:396-406.
53. Jones K.B., Piombo V., Searby C., et al. A mouse model of osteochondromagenesis from clonal inactivation of Ext1 in chondrocytes. Proc Natl Acad Sci USA 2010, 107:2054-2059.
54. de Andrea C.E., Wiweger M., Prins F., et al. Primary cilia organization reflects polarity in the growth plate and implies loss of polarity and mosaicism in osteochondroma. Lab Invest 2010, 90:1091-1101.
55. Clément A., Wiweger M., von der Hardt S., et al. Regulation of zebrafish skeletogenesis by ext2/dackel and papst1/pinscher. PLoS Genet 2008, 4:e1000136.
56. Bovee J.V.M.G. EXTra hit for mouse osteochondroma. Proc Natl Acad Sci USA 2010, 107:1813-1814.
57. de Andrea C.E., Reijnders C.M., Kroon H.M., et al. Secondary peripheral chondrosarcoma evolving from osteochondroma as a result of outgrowth of cells with functional EXT. Oncogene 2011, 31:1095-1104.
58. Amary M.F., Damato S., Halai D., et al. Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nat Genet 2011, 43:1262-1265.
59. Arai M., Nobusawa S., Ikota H., Takemura S., Nakazato Y. Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma. Brain Tumor Pathol 2012, [Epub ahead of print].
60. Damato S., Alorjani M., Bonar F., et al. IDH1 mutations are not found in cartilaginous tumours other than central and periosteal chondrosarcomas and enchondromas. Histopathology 2012, 60:363-365.
61. Schrage Y.M., Lam S., Jochemsen A.G., et al. Central chondrosarcoma progression is associated with pRb pathway alterations; CDK4 downregulation and p16 overexpression inhibit cell growth in vitro. J Cell Mol Med 2008, 13:2843-2852.
62. van Beerendonk H.M., Rozeman L.B., Taminiau A.H.M., et al. Molecular analysis of the INK4A/INK4A-ARF gene locus in conventional (central) chondrosarcomas and enchondromas: indication of an important gene for tumour progression. J Pathol 2004, 202:359-366.
63. Bovee J.V.M.G., Van den Broek L.J.C.M., Cleton-Jansen A.M., et al. Up-regulation of PTHrP and Bcl-2 expression characterizes the progression of osteochondroma towards peripheral chondrosarcoma and is a late event in central chondrosarcoma. Lab Invest 2000, 80:1925-1933.
64. Rozeman L.B., Hameetman L., Cleton-Jansen A.M., et al. Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas. J Pathol 2005, 205:476-482.
65. Schrage Y.M., Hameetman L., Szuhai K., et al. Aberrant heparan sulfate proteoglycan localization, despite normal exostosin, in central chondrosarcoma. Am J Pathol 2009, 174:979-988.
66. Tiet T.D., Hopyan S., Nadesan P., et al. Constitutive hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation. Am J Pathol 2006, 168:321-330.
67. Schrage Y.M., Briaire-de Bruijn I.H., de Miranda N.F.C.C., et al. Kinome profiling of chondrosarcoma reveals Src-pathway activity and dasatinib as option for treatment. Cancer Res 2009, 69:6216-6222.
68. Grignani G., Palmerini E., Stacchiotti S., et al. A phase 2 trial of imatinib mesylate in patients with recurrent nonresectable chondrosarcomas expressing platelet-derived growth factor receptor-alpha or -beta: An Italian Sarcoma Group study. Cancer 2011, 117:826-831.
69. Ho L., Stojanovski A., Whetstone H., et al. Gli2 and p53 cooperate to regulate IGFBP-3-mediated chondrocyte apoptosis in the progression from benign to malignant cartilage tumors. Cancer Cell 2009, 16:126-136.
70. Meijer D., Gelderblom H., Karperien M., et al. Expression of aromatase and estrogen receptor alpha in chondrosarcoma, but no beneficial effect of inhibiting estrogen signaling both in vitro and in vivo. Clin Sarcoma Res 2011, 1:5. 10.1186/2045-3329-1-5.
71. Cleton-Jansen A.M., van Beerendonk H.M., Baelde H.J., et al. Estrogen signaling is active in cartilaginous tumors: implications for antiestrogen therapy as treatment option of metastasized or irresectable chondrosarcoma. Clin Cancer Res 2005, 11:8028-8035.
72. Boeuf S., Bovee J.V.M.G., Lehner B., et al. Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours. Histopathology 2010, 56:641-651.
73. Rozeman L.B., Hameetman L., van Wezel T., et al. cDNA expression profiling of central chondrosarcomas: Ollier disease resembles solitary tumors and alteration in genes coding for energy metabolism with increasing grade. J Pathol 2005, 207:61-71.
74. van Oosterwijk J.G., Herpers B., Meijer D., et al. Restoration of chemosensitivity for doxorubicin and cisplatin in chondrosarcoma in vitro: BCL-2 family members cause chemoresistance. Ann Oncol 2011 Nov 23, [epub ahead of print]; doi:10.1093/annonc/mdr512.
75. Romeo S., Hogendoorn P.C. Brachyury and chordoma: the chondroid-chordoid dilemma resolved?. J Pathol 2006, 209:143-146.
76. Vujovic S., Henderson S., Presneau N., et al. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 2006 Jun, 209:157-165.
77. Hazelbag H.M., Van den Broek L.J.C.M., Van Dorst E.B.L., et al. Immunostaining of chain-specific keratins on formalin-fixed, paraffin-embedded tissues: A comparison of various antigen retrieval systems using microwave heating and proteolytic pre-treatments. J Histochem Cytochem 1995, 43:429-437.
78. Hallor K.H., Staaf J., Jonsson G., et al. Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation. Br J Cancer 2008, 98:434-442.
79. Yang X.R., Ng D., Alcorta D.A., et al. T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet 2009, 41:1176-1178.
80. Presneau N., Shalaby A., Ye H., et al. Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study. J Pathol 2011, 223:327-335.
81. Sandberg A.A., Bridge J.A. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: chondrosarcoma and other cartilaginous neoplasms. Cancer Genet Cytogenet 2003, 143:1-31.
82. Stephens P.J., Greenman C.D., Fu B., et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 2011, 144:27-40.
83. Atiye J., Wolf M., Kaur S., et al. Gene amplifications in osteosarcoma-CGH microarray analysis. Genes Chromosomes Cancer 2005, 42:158-163.
84. Lau C, Man TK, Visvanathan J, et al. Molecular profiles of osteosarcoma that can predict response to chemotherapy. In: Proceedings of the Connective Tissue Oncology Society, 9th annual meeting. Montreal, Canada, 2004 Nov 11-13.
85. Ozaki T., Schaefer K.L., Wai D., et al. Genetic imbalances revealed by comparative genomic hybridization in osteosarcomas. Int J Cancer 2002, 102:355-365.
86. Squire J.A., Pei J., Marrano P., et al. High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer 2003, 38:215-225.
87. Stock C., Kager L., Fink F.M., et al. Chromosomal regions involved in the pathogenesis of osteosarcomas. Genes Chromosomes Cancer 2000, 28:329-336.
88. Lim G., Karaskova J., Beheshti B., et al. An integrated mBAND and submegabase resolution tiling set (SMRT) CGH array analysis of focal amplification, microdeletions, and ladder structures consistent with breakage-fusion-bridge cycle events in osteosarcoma. Genes Chromosomes Cancer 2005, 42:392-403.
89. Selvarajah S., Yoshimoto M., Ludkovski O., et al. Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase FISH. Cytogenet Genome Res 2008, 122:5-15.
90. Nielsen G.P., Burns K.L., Rosenberg A.E., et al. CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations. Am J Pathol 1998, 153:159-163.
91. Wei G., Lonardo F., Ueda T., et al. CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons. Int J Cancer 1999, 80:199-204.
92. Wunder J.S., Gokgoz N., Parkes R., et al. TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study. J Clin Oncol 2005, 23:1483-1490.
93. Overholtzer M., Rao P.H., Favis R., et al. The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc Natl Acad Sci USA 2003, 100:11547-11552.
94. Miller C.W., Ikezoe T., Krug U., et al. Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. Genes Chromosomes Cancer 2002, 33:17-21.
95. Mohseny A.B., Szuhai K., Romeo S., et al. Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol 2009, 219:294-305.
96. Ulaner G.A., Huang H.Y., Otero J., et al. Absence of a telomere maintenance mechanism as a favorable prognostic factor in patients with osteosarcoma. Cancer Res 2003, 63:1759-1763.
97. Sanders R.P., Drissi R., Billups C.A., et al. Telomerase expression predicts unfavorable outcome in osteosarcoma. J Clin Oncol 2004, 22:3790-3797.
98. Kido A., Schneider-Stock R., Hauptmann K., et al. Telomerase activity in juxtacortical and conventional high-grade osteosarcomas: correlation with grade, proliferative activity and clinical response to chemotherapy. Cancer Lett 2003, 196:109-115.
99. Buddingh' E.P., Kuijjer M.L., Duim R.A., et al. Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage-activating agents. Clin Cancer Res 2011, 17:2010-2019.