USP6 rearrangement is the most common genetic abnormality in primary aneurysmal bone cyst,
and SS18 rearrangement has not been previously described in any type of tumor where synovial
sarcoma was excluded from the differential diagnosis. We report a case of solid aneurysmal
bone cyst in which fluorescence in situ hybridization (FISH) analysis indicated rearrangements
of both USP6 and SS18, but histologic features were consistent with aneurysmal bone cyst throughout the
lesion. Reverse-transcription polymerase chain reaction (RT-PCR) for the SS18-SSX1 and SS18-SSX2 translocations, identity testing, and SS18 FISH were performed on cytogenetic monolayer cultures and formalin-fixed paraffin-embedded
(FFPE) tissue. Genomic microarray, FISH, and immunohistochemistry were performed on
follow-up studies of the FFPE specimen. The karyotype was 45,X,add(X)(p11.2),add(4)(q13),add(8)(p21),-13,add(17)(p11.2),add(18)(q11.2)
in all 20 cells analyzed from monolayer cultures. The karyotype showed no cytogenetically
visible alterations of chromosomal regions harboring known partners for USP6. Metaphase FISH with a commercial SS18 break-apart probe showed translocation of the 5′ portion of the SS18 probe to the short arm of the derivative X, as is observed in synovial sarcoma. RT-PCR
showed no evidence of a SS18-SSX fusion, and immunohistochemistry was negative for TLE1, EMA, and cytokeratin AE1/3
expression. FISH on FFPE sections with a custom break-apart probe flanking USP6 showed evidence for a USP6 rearrangement throughout the tumor (25–50%). FISH on FFPE sections with a commercial
SS18 break-apart FISH probe showed more variable results (0–50% split signals). There
was no evidence of a SS18-USP6 fusion by FISH or RT-PCR. A molecular inversion probe array revealed a deletion encompassing
the entire SS18 gene and its promoter, as well as portions of the region targeted by the commercial
SS18 FISH probe. In conclusion, results obtained from commercially available FISH probes
may occasionally yield misleading results. In this case, the SS18 rearrangement by FISH resulted from a complex rearrangement of 18q11.2 with a deletion
of the SS18 gene. The translocation partner for USP6 remains unknown in this case.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Cancer GeneticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Conditions that commonly simulate primary neoplasms of bone.in: Unni K.K. Inwards C. Dahlin’s bone tumors general aspects and data on 10,165 cases. 6th Ed. Lippincott-Raven, Philadelphia2009 (pp. 305–380)
- Bone Tumors of miscellaneous or uncertain lineage.in: Folpe A. Inwards C. Bone and Soft Tissue Pathology. Saunders Elsevier, Philadelphia2010 (pp. 428–432)
- Aneurysmal bone cyst: concept, controversy, clinical presentation, and imaging.Am J Roentgenol. 1995; 164: 573-580
- Metastatic potential of an aneurysmal bone cyst.Virchows Arch. 2009; 455: 455-459
- Aneurysmal bone cyst: a review of 150 patients.J Clin Oncol. 2005; 23: 6756-6762
- Aneurysmal bone cyst.Am J Clin Oncol. 2006; 29: 311-315
- Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts.Genes Chromosomes Cancer. 1999; 26: 265-266
- Variant translocations involving 16q22 and 17p13 in solid variant and extraosseous forms of aneurysmal bone cyst.Genes Chromosomes Cancer. 2000; 28: 233-234
- Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group.Mod Pathol. 2000; 13: 1206-1210
- Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization.Mod Pathol. 2004; 17: 518-525
- USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst.Cancer Res. 2004; 64: 1920-1923
- 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
- Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes.Oncogene. 2005; 24: 3419-3426
- TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB.Oncogene. 2010; 29: 3619-3629
- Solid variant of aneurysmal bone cyst with a novel (X;9) translocation.Cancer Genet Cytogenet. 2007; 178: 155-159
- Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma.Mod Pathol. 2007; 20: 482-496
- Allele quantification using molecular inversion probes (MIP).Nucleic Acids Res. 2005; 33: e183
- Analysis of molecular inversion probe performance for allele copy number determination.Genome Biol. 2007; 8: R246
- Molecular inversion probes reveal patterns of 9p21 deletion and copy number aberrations in childhood leukemia.Cancer Genet Cytogenet. 2009; 193: 9-18
- Prospective evaluation of TLE1 as a diagnostic immunohistochemical marker in synovial sarcoma.Am J Surg Pathol. 2009; 33: 1743-1751
- TLE1 is a robust diagnostic biomarker for synovial sarcomas and correlates with t(X;18): analysis of 319 cases.Eur J Cancer. 2010; 46: 1170-1176
- Novel SYT-SSX fusion transcript variants in synovial sarcoma.Cancer Genet Cytogenet. 2009; 195: 54-58
- Fluorescence in situ hybridization in the diagnosis of soft tissue neoplasms: a review.Adv Anat Pathol. 2009; 16: 383-391
- Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients.Cancer Res. 2002; 62: 135-140
- Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma.Am J Pathol. 1996; 148: 559-567
- Cancer Cytogenetics.Wiley-Blackwell, Hoboken, NJ2009
- The impact of translocations and gene fusions on cancer causation.Nat Rev Cancer. 2007; 7: 233-245
Article info
Publication history
Accepted:
January 27,
2011
Received in revised form:
December 12,
2010
Received:
March 11,
2010
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
