Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

Abstract

Aneurysmal bone cyst is a benign, cystic lesion of bone composed of blood-filled spaces separated by fibrous septa. Relatively few cases of aneurysmal bone cyst have been cytogenetically characterized, yet abnormalities of the short arm of chromosome 17 appear to be recurrent. In this study, conventional cytogenetic analysis of 43 aneurysmal bone cyst specimens from 38 patients over a 12-year period revealed clonal chromosomal abnormalities in 12 specimens. Karyotypic anomalies of 17p, including a complex translocation and inversion, were identified in eight of these 12 specimens. In an effort to further define the aberrant 17p breakpoint, fluorescence in situ hybridization (FISH) analyses were performed using a series of probe combinations spanning a 5.1 Mb region between the TP53 (17p13.1) and Miller-Dieker lissencephaly syndrome (17p13.3) gene loci. These studies revealed the critical breakpoint locus at 17p13.2, flanked proximally by an RP11-46I8, RP11-333E1, and RP11-457I18 bacterial artificial chromosome (BAC) probe cocktail and distally by an RP11-198F11 and RP11-115H24 BAC and RP5-1050D4 P1 artificial chromosome (PAC) probe cocktail. Overall, abnormalities of the 17p13.2 locus were identified by metaphase and/or interphase cell FISH analysis in 22 of 35 (63%) aneurysmal bone cyst specimens examined including 26 karyotypically normal specimens. These cytogenetic and molecular cytogenetic findings expand our knowledge of chromosomal alterations in aneurysmal bone cyst, further localize the critically involved 17p breakpoint, and provide an alternative approach (ie FISH) for detecting 17p abnormalities in nondividing cells of aneurysmal bone cysts. The latter could potentially be utilized as an adjunct in diagnostically challenging cases.

Percutaneous Doxycycline Treatment of Aneurysmal Bone Cysts With Low Recurrence Rate: A Preliminary Report

“…ABCs demonstrate specific translocational events, most commonly found on chromosomal bands 16q22 and 17p13 with TRE17/ubiquitin carboxyl-terminal hydrolase 6 (USP6) oncogene rearrangements found in primary ABCs [2,3,10,[30][31][32]38]. Multinucleated giant cells in ABCs express osteolytic features of osteoclasts with high levels of matrix metalloproteinases (MMP-9 and MMP-10), tartarate-resistant acid phosphatase, and cathepsin K [23,26].…”

Aneurysmal Bone Cyst of the Patella

“…ZNF9 -USP6, t(9;17)(q22;p13) OMD -USP6, t(17;17)(q12;p13) COL1A1 -USP6. Although additional cases should be studied, it appears that in combined giant cell tumor and secondary aneurysmal bone cyst, both lesions can retain their characteristic chromosomal aberrations 6) .…”

A novel t(4;22)(q31;q12) produces an EWSR1–SMARCA5 fusion in extraskeletal Ewing sarcoma/primitive neuroectodermal tumor

“…Hybridization was conducted as previously described. 27 Hybridization signals were assessed in five metaphase cells or 200 interphase nuclei with strong, well-delineated signals by two different individuals. As a negative control, FISH studies were simultaneously conducted on karyotypically normal peripheral-blood lymphocytes.…”