USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts.
Aneurysmal bone cyst (ABC) is a locally recurrent bone lesion that has been regarded as a reactive process. Recently, a neoplastic basis in primary ABC was evidenced by demonstration of clonal chromosome band 17p13 translocations that place the USP6 (TRE2 or TRE17) oncogene under the regulatory influence of the highly active CDH11 promoter. Herein, we report CDH11 and/or USP6 rearrangements in 36 of 52 primary ABCs (69%), of which 10 had CDH11-USP6 fusion, 23 had variant USP6 rearrangements without CDH11 rearrangement, and three had variant CDH11 rearrangements without USP6 rearrangement. USP6 and CDH11 rearrangements were restricted to spindle cells in the ABC and were not found in multinucleated giant cells, inflammatory cells, endothelial cells, or osteoblasts. CDH11 and USP6 rearrangements did not correlate with recurrence-free survival, or with other clinicopathological features. CDH11 and USP6 rearrangements were not found in any of 17 secondary ABC associated with giant cell tumor, chondroblastoma, osteoblastoma, and fibrous dysplasia. These findings demonstrate that primary ABC are mesenchymal neoplasms exhibiting USP6 and/or CDH11 oncogenic rearrangements. By contrast, secondary ABC lack CDH11 and USP6 rearrangements, and although morphological mimics of primary ABC, appear to represent a non-specific morphological pattern of a diverse group of non-ABC neoplasms.
Oliveira
Andre M
AM
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. oliveira.andre@mayo.edu
Perez-Atayde
Antonio R
AR
Inwards
Carrie Y
CY
Medeiros
Fabiola
F
Derr
Victoria
V
Hsi
Bae-Li
BL
Gebhardt
Mark C
MC
Rosenberg
Andrew E
AE
Fletcher
Jonathan A
JA
D000293:Adolescent; D000328:Adult; D017824:Bone Cysts, Aneurysmal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics* / Q000502:physiology*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D010450:Endopeptidases / Q000235:genetics* / Q000502:physiology*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007249:Inflammation; D008297:Male; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D043222:Ubiquitin Thiolesterase
D015820:Cadherins; C502403:FAT1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012313:RNA; D010450:Endopeptidases; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase