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Solid Tumour Section
Mini Review
Bone: Aneurysmal bone cysts
Paola Dal Cin
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA (PD)
Published in Atlas Database: June 2004
Online updated version: http://AtlasGeneticsOncology.org/Tumors/AneurBoneCystID5133.html
DOI: 10.4267/2042/38115
This article is an update of : Dal Cin P. Bone: Aneurysmal bone cysts. Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):134-135.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2004 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Clinics and pathology
Treatment
Etiology
ABC is most frequently treated by curettage, but local
recurrences can still occur in a substantial number of
cases.
The most widely accepted pathogenetic mechanism of
aneurysmal bone cysts involves a local circulatory
disturbance leading to markedly increased venous
pressure and the development of a dilated and enlarged
vascular bed within the affected bone area. However,
the recent identifica-tion of recurrent chromosome
abnormalities has challenged this historical perception.
Cytogenetics
Cytogenetics Morphological
Chromosome bands 16q22 and/or 17p13 are non
randomly rearranged in ABC, regardless of tumor type
(classic, solid) and or location (osseous and
extraosseous). A recurrent t(16;17)(q22;p13) has been
identified, but other chromosomal segments as
translocation partner for each chromosome have been
described:
t(1;17)(p34;p13)
THRAP3
-USP6,
t(3;17)(q21;p13) 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.
Clinics
Aneurysmal bone cysts (ABC) are benign lesions that
occur more frequently in the metaphyses of long bones,
especially distal femur, the proximal tibia and vertebral
posterior bodies. It can occur at any age but most
patients are diagnosed in the first 2 decades of life. It
can exist as primary bone lesion or as secondary lesions
arising in association with other osseous conditions,
namely
giant
cell
tumor,
chondroblastoma,
chondromyxoid fibroma and fibrous dysplasia. Pain
and swelling are the most common complaints.
Pathology
Genes involved and proteins
As the name implies, the lesion is histopa-thologically
characterized by hemorrhagic cystic and cavernous
spaces surrounded by fibrous septa composed of mildly
to moderately mitotically active spindle cells
intermixed with scattered osteoclast-like multinucleated
giant cells. Approxi-mately 95% of ABC have typical
histology whereas the remaining 5% are "solid"
variants in which the usual cavernous channels and
spaces may not be identified. An extraosseous
couterpart of ABC has been described, sometimes
referred to as ABC of soft tissues, and is histologically
identical to ABC but diagnosed much less frequently.
USP6 (Ubiquitin Specific Protease 6).
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
Also known as TRE-2 or TRE17.
Location
17p13
DNA / RNA
7878 bp (major transcript).
Protein
786 amino acids; USP6 is a hominoid-specific gene
that was initially cloned form an Ewing sarcoma cell
line. It arose from an evolutionary chimeric gene fusion
261
Bone: Aneurysmal bone cysts
Dal Cin P
between the TBC1D3 (also known as PRC17) and
USP32 (NY-REN-60) genes, which are both located on
the long arm of chromosome 17. Sequence
comparisons indicate that the first 14 exons of USP6
are derived from TBC1D3 (PRC17) whereas exons 15
to 30 are derived from USP32 (10). TBC1D3 (PRC17)
is located at chromosome band 17q12 and encodes a
protein with a TBC/GAP domain involved in Rab/Ypt
GTPase signaling. USP32 is located at chromosome
band 17q23 and encodes a protein composed of two
EF-hand calcium-binding motifs, a myristoylation site,
and a UBP domain. USP6 protein retains the TBC
domain of TBC1D3 (PRC17) and the UBP domain of
USP32. Because USP6 is absent in non-hominoid
primates and is primarily expressed in testicular tissue,
it has been suggested that USP6 contributed to
hominoid speciation. Until recently USP6 function was
poorly know but recent data suggest that USP6 is a
component of a novel effector pathway for Rho
GTPases Cdc42 and Rac1 and stimulates actin
remodeling.
Oncogenesis
The oncogenic mechanism of CDH11-USP6 is still
unknown but very likely involves transcription
upregulation of USP6 mediated by the highly active
CDH11 promoter.
References
Pfeifer FM, Bridge JA, Neff JR, Mouron BJ. Cytogenetic
findings in aneurysmal bone cysts. Genes Chromosomes
Cancer. 1991 Nov;3(6):416-9
Bertoni F, Bacchini P, Capanna R, Ruggieri P, Biagini R,
Ferruzzi A, Bettelli G, Picci P, Campanacci M. Solid variant of
aneurysmal bone cyst. Cancer. 1993 Feb 1;71(3):729-34
Rodríguez-Peralto JL, López-Barea F, Sánchez-Herrera S,
Atienza M. Primary aneurysmal cyst of soft tissues
(extraosseous aneurysmal cyst) Am J Surg Pathol. 1994
Jun;18(6):632-6
Dal Cin P, Kozakewich HP, Goumnerova L, Mankin HJ,
Rosenberg AE, Fletcher JA. Variant translocations involving
16q22 and 17p13 in solid variant and extraosseous forms of
aneurysmal bone cyst. Genes Chromosomes Cancer. 2000
Jun;28(2):233-4
CDH11 (Cadherin 11 or Osteoblast
Cadherin or OB-Cadherin)
Sciot R, 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, Tallini G, Van den Berghe H, Vanni R,
Willén H. 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
Nov;13(11):1206-10
Location
16q21-q22.1
DNA / RNA
3.6 and 3.8 kb mRNA (two major transcripts).
Protein
693 and 796 amino acids; Membrane protein that
mediate calcium-dependent cell-cell adhesion, member
of the cadherin superfamily. CDH11 seems to be highly
expressed during the development and differentiation
of the osteoblastic lineage, indicating an important role
in bone development. Two splice variants have been
identified, one of which encodes an isoform with a
shorter cytoplasmic domain.
Baruffi MR, Neto JB, Barbieri CH, Casartelli C. Aneurysmal
bone cyst with chromosomal changes involving 7q and 16p.
Cancer Genet Cytogenet. 2001 Sep;129(2):177-80
Herens C, Thiry A, Dresse MF, Born J, Flagothier C,
Vanstraelen G, Allington N, Bex V. Translocation
(16;17)(q22;p13) is a recurrent anomaly of aneurysmal bone
cysts. Cancer Genet Cytogenet. 2001 May;127(1):83-4
Winnepenninckx V, Debiec-Rychter M, Jorissen M, Bogaerts
S, Sciot R. Aneurysmal bone cyst of the nose with 17p13
involvement. Virchows Arch. 2001 Nov;439(5):636-9
Wyatt-Ashmead J, Bao L, Eilert RE, Gibbs P, Glancy G,
McGavran L. Primary aneurysmal bone cysts: 16q22 and/or
17p13 chromosome abnormalities. Pediatr Dev Pathol. 2001
Jul-Aug;4(4):418-9
Result of the chromosomal
anomaly
Nielsen GP, Fletcher CD, Smith MA, Rybak L, Rosenberg AE.
Soft tissue aneurysmal bone cyst: a clinicopathologic study of
five cases. Am J Surg Pathol. 2002 Jan;26(1):64-9
Hybrid Gene
Description
5’ CDH11 - 3’ USP6.
Althof PA, Ohmori K, Zhou M, Bailey JM, Bridge RS, Nelson M,
Neff JR, Bridge JA. 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 May;17(5):518-25
Fusion Protein
Description
Fusion of the promoter region of CDH11 (noncoding
exons 1 and 2) to the entire coding region of USP6,
which starts on exon 2. Therefore, there is only a fusion
gene but not a fusion protein. This type of gene fusion
is known as promoter swapping and has been described
in other solid tumors, including pleomorphic adenoma
and lipoblastoma.
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
Oliveira AM, Hsi BL, Weremowicz S, Rosenberg AE, Dal Cin
P, Joseph N, Bridge JA, Perez-Atayde AR, Fletcher JA. USP6
(Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer
Res. 2004 Mar 15;64(6):1920-3
Oliveira AM, Hsi BL, Weremowicz S, Rosenberg AE, Dal Cin
P, Joseph N, Bridge JA, Perez-Atayde AR, Fletcher JA. USP6
(Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer
Res. 2004 Mar 15;64(6):1920-3
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Bone: Aneurysmal bone cysts
Dal Cin P
Oliveira AM, Perez-Atayde AR, Inwards CY, Medeiros F, Derr
V, Hsi BL, Gebhardt MC, Rosenberg AE, Fletcher JA. 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 Nov;165(5):177380
JA. Aneurysmal bone cyst variant translocations upregulate
USP6 transcription by promoter swapping with the ZNF9,
COL1A1, TRAP150, and OMD genes. Oncogene. 2005 May
12;24(21):3419-26
Oliveira AM, Perez-Atayde AR, Dal Cin P, Gebhardt MC, Chen
CJ, Neff JR, Demetri GD, Rosenberg AE, Bridge JA, Fletcher
Dal Cin P. Bone: Aneurysmal bone cysts. Atlas Genet
Cytogenet Oncol Haematol. 2004; 8(3):261-263.
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
This article should be referenced as such:
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