Bone: Aneurysmal bone cyst with t(3;17)(q21;p13) CNBP/USP6

2011-11-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Note

Benign but locally aggressive tumor.

Phenotype stem cell origin

Occurs mainly in vertebrae and flat bones. Multiple involvement is frequent.

Etiology

May involve the arrest of maturation of the osteoblasts caused by USP6 overexpression and dysregulation of autocrine BMP (bone morphology protein) signaling (Lau et al., 2010).

Epidemiology

Usually seen in patients aged 10-20 years; represents about 5% of primary bone tumours; slightly more frequent in female patients.

Clinics

Forms a spongy hemorrhagic mass; symptoms are pain, swelling, pathological fractures. One case to date was found with a t(3;17)(q21;p13), a 7-year-old girl with a tumor located in the tibia (Oliveira et al., 2005).

Treatment

Surgical curetage.

Prognosis

Recurrence occurs in one fourth of cases.

Cytogenetics

Cytogenetics morphological

The t(3;17)(q21;p13) was the sole anomaly.

Genes Involved and Proteins

Gene name

CNBP (CCHC-type zinc finger nucleic acid binding protein)

Location

3q21.3

Protein description

CNBP, also called ZNF9, is made of 7 CCHC-type Zn fingers. Nucleic acid binding protein; binds single stranded DNA and RNA; act as a regulator of transcription and translation of many genes, including MYC. CNBP may regulate gene expression by catalyzing the formation of G4s (G-quadruplexes, formed by intramolecular four-stranded DNA structures).

Germinal mutations

Myotonic dystrophy DM2 is caused by expansion of a (CCTG)(n) in CNBP. CNBP has also been implicated in sporadic inclusion body myositis (review in Calcaterra et al., 2010).

Gene name

USP6 (ubiquitin specific protease 6 (Tre-2 oncogene))

Location

17p13.2

Protein description

USP6, also called TRE17/ubiquitin-specific protease 6 (USP6), is a deubiquitinase. It is the first de-ubiquitinating enzyme to activate NF-KB, and requires both catalytic subunits of IKK (IKKalpha and IKKbeta) (Pringle et al., 2011).

Result of the chromosomal anomaly

Description

5 CNBP - 3 USP6

Description

Fusion of the noncoding exon 1 of CNBP to USP exon 2 (i.e. to the entire coding sequence of USP6, resulting in upregulation of USP6).

Bibliography

Pubmed IDLast YearTitleAuthors
209605302010CNBP: a multifunctional nucleic acid chaperone involved in cell death and proliferation control.Calcaterra NB et al
208645342010TRE17/ubiquitin-specific protease 6 (USP6) oncogene translocated in aneurysmal bone cyst blocks osteoblastic maturation via an autocrine mechanism involving bone morphogenetic protein dysregulation.Lau AW et al
157356892005Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes.Oliveira AM et al
220810692012Atypical mechanism of NF-κB activation by TRE17/ubiquitin-specific protease 6 (USP6) oncogene and its requirement in tumorigenesis.Pringle LM et al

Citation

Jean-Loup Huret

Bone: Aneurysmal bone cyst with t(3;17)(q21;p13) CNBP/USP6

Atlas Genet Cytogenet Oncol Haematol. 2011-11-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/5671/bone-aneurysmal-bone-cyst-with-t(3;17)(q21;p13)-cnbp-usp6