Download Solid Tumour Section Soft tissue chondroma with t(3;12)(q27;q15) in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Solid Tumour Section
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Soft tissue chondroma with t(3;12)(q27;q15)
Anna Collin
Department of Clinical Genetics, Lund University Hospital, 221 85 Lund, Sweden
Published in Atlas Database: October 2006
Online updated version: http://AtlasGeneticsOncology.org/Tumors/Chondromat0312ID5428.html
DOI: 10.4267/2042/38391
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2007 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Cytogenetics molecular
Clinics and pathology
Metaphase FISH mapping using cosmid probes specific
for exons 1-2 (142H1) and exons 4-5 (27E12) of
HMGA2 revealed that the breakpoint in chromosome
band 12q15 was located within the large intron 3 of
HMGA2.
Note: Only one case has been described to date.
Disease
Soft tissue chondroma with t(3;12)(q27;q15)
Embryonic origin
Genes involved and Proteins
The embryonic origin is unknown, but the tumor cells
presumably derive from the mesoderm.
HMGA2 (high mobility group AT-hook 2)
Etiology
Location: 12q15
DNA/RNA
The gene consists of 5 exons that span approximately
160 kb of genomic DNA in the centromere-to-telomere
orientation. The first three exons are separated from the
last two exons by a particularly large intron (about 112
kb). The corresponding transcript is approximately 4,1
kb (referred to as 'wildtype' or 'isoform a' transcript of
HMGA2). The translation initiation codon ATG is
located in exon 1 and the stop codon in exon 5.
Several alternative splice products of HMGA2 have
been reported (referred to as 'isoforms b, c, d, e and f'
transcripts of HMGA2, respectively).
Protein
The open reading frame encodes a 108 amino acid
protein with an estimated molecular weight of
approximately 12 kDa.
The first 3 exons each encode a DNA-binding domain.
Exons 4 and 5 encode a spacer domain and an acidic
domain, respectively. It has been suggested that the 3'UTR acts as a negative regulator of the expression of
HMGA2.
The HMGA2 protein is a member of the HMGA (high
mobility group A) family of proteins and is believed to
affect transcription as architectural elements by
bending the DNA and by interacting with a large
Unknown.
Epidemiology
The only case of soft tissue chondroma with
t(3;12)(q27;q15) described to date was a tumor resected
from a 62-year-old man.
Clinics
The tumor presented as a solitary mass (8 x 6 x 8 cm)
in the elbow region (fossa cubiti).
Pathology
The tumor displayed a multilobulated growth pattern
and was composed of mature adult hyaline cartilage
with peripheral areas of myxofibromatous/lipomatous
tissue and metaplastic bone tissue.
Treatment
The tumor was removed with marginal excision.
Cytogenetics
Cytogenetics morphological
The t(3;12)(q27;q15) has so far been described in one
case of soft tissue chondroma. The same translocation
has been identified as a recurrent chromosomal
aberration in ordinary lipoma and pulmonary chondroid
hamartoma.
Atlas Genet Cytogenet Oncol Haematol. 2007;11(1)
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Soft tissue chondroma with t(3;12)(q27;q15)
Collin A
number of proteins, mainly transcription factors.
Reported specific targets of the HMGA2 protein are the
pRB protein, as well as the promoter regions of the
DNA-repair gene ERCC1 and the cyclin A gene.
Detection protocole
Several detailed protocols for the detection of the
HMGA2-LPP fusion transcript have been published.
Fusion Protein
LPP (LIM domain containing preferred
translocation partner in lipoma)
Note: The HMGA2-LPP fusion protein has not been
functionally studied in soft tissue chondroma with
t(3;12)(q27;q15).
Description
The HMGA2-LPP fusion protein is composed of the
DNA-binding domains of HMGA2 and the LIM2 and
LIM3 domains of LPP.
Expression Localisation
In transfection assays of 3T3-L1 cells it has been
shown that the HMGA2-LPP fusion protein is located
in the nucleus.
Oncogenesis
It has been suggested that the abnormal tumor cell
proliferation is caused by a disruption in the balance of
co-expression between the wildtype HMGA2 transcript
and its splice variants.
Location: 3q27-28
DNA/RNA
The gene consists of 11 exons and spans approximately
667 kb of genomic DNA in the centromere-to-telomere
orientation.
The
corresponding
transcript
is
approximately 7,3 kb. The translation initiation codon
is located in exon 3 and the stop codon in exon 11.
Protein
The open reading frame encodes a 612 amino acid
protein.
The protein is composed of a proline rich N-terminal
and 3 LIM domains in its C-terminal. Exons 3-7 encode
the proline-rich domain. Exon 8 encodes the LIM1
domain and exon 9 encodes the LIM2 domain. Exon 10
and parts of exon 11 encode the LIM3 domain.
The LPP protein is a member of the zyxin family (also
referred to as 'group 3') of LIM domain proteins. The
LIM-domain encodes a double zink finger motif
involved in protein-protein interactions. Functionally
the LPP protein interacts with cytoplasmic proteins
involved in focal adhesion and cell-to-cell contact, but
it does also shuttle between the cytoplasm and the
nucleus and has therefore been attributed a role in
signal transduction processes. It has recently been
shown that the LIM domains of LPP function as a
transcriptional coactivator of the transcription factor
PEA3/ ETV4.
References
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Note: Only one case has been described to date.
Description
The structure of the hybrid gene has not been
investigated at the genomic level in soft tissue
chondroma with t(3;12)(q27;q15).
Transcript
The detected HMGA2-LPP fusion transcript was
composed of the first 3 exons of HMGA2 and exons 911 of LPP. Identical fusion transcripts have previously
been detected in ordinary lipoma and pulmonary
chondroid hamartoma. The findings of identical fusion
transcripts in different tumor types have strengthened
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This article should be referenced as such:
Collin A. Soft tissue chondroma with t(3;12)(q27;q15). Atlas
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Tessari MA, Gostissa M, Altamura S, Sgarra R, Rustighi A,
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Giancotti V, Manfioletti G. Transcriptional activation of the
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