Download Solid Tumour Section Soft tissue tumors: t(2;2)(p23;q35) in alveolar rhabdomyosarcoma

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Solid Tumour Section
Short Communication
Soft tissue tumors: t(2;2)(p23;q35) in alveolar
rhabdomyosarcoma
Frederic G Barr
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine,
Philadelphia, PA 19104, USA (FGB)
Published in Atlas Database: July 2010
Online updated version : http://AtlasGeneticsOncology.org/Tumors/t22p23q35AlvRhabdoID5445.html
DOI: 10.4267/2042/45009
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2011 Atlas of Genetics and Cytogenetics in Oncology and Haematology
NCOA1
Clinics and pathology
Location
2p23
Protein
Nuclear receptor transcriptional coactivator - p160
family.
Phenotype / cell stem origin
Alveolar rhabdomyosarcoma (ARMS).
Epidemiology
Occurs in a small subset of ARMS cases (<5%). There
are five reported cases.
PAX3
Pathology
Location
2q35
Note
The NCOA2 gene (encoding another member of the
p160 family of transcriptional coactivators) is located
at 8q13 and involved in the variant t(2;8).
Protein
Transcription factor - paired box (PAX) family.
No information available.
Cytogenetics
Cytogenetics Morphological
Of the five reported cases, cytogenetics was only
performed on one case and demonstrated a normal
karyotype.
Result of the chromosomal
anomaly
Cytogenetics Molecular
Several of these cases were detected using fluorescence
in situ hybridization analysis by the finding of PAX3
rearrangement without evidence of a PAX3-FOXO1
fusion or FOXO1 rearrangement. Other cases were
detected by directly assaying cases with a PAX3NCOA1 fusion-specific RT-PCR assay.
Hybrid Gene
Description
Based on the cloned cDNA, there appears to be two
possible scenarios for formation of fusion genes. In
some cases, the translocation apparently breaks within
PAX3 intron 6 and NCOA1 intron 12 (type 1), and in
other cases the translocation breaks within PAX3 intron
7 and NCOA1 intron 11 (type 2).
Transcript
The type 1 fusion transcript consists of the first six
PAX3 exons fused to the last nine NCOA1 exons
Genes involved and proteins
Note
A variant t(2;8)(q35;q13) translocation has been
identified, both in ARMS and in cases of embryonal
rhabdomyosarcoma.
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(4)
385
Soft tissue tumors: t(2;2)(p23;q35) in alveolar rhabdomyosarcoma
Barr FG
Generation of chimeric genes by the 2;2 translocation in ARMS. The exons of the wild-type and fusion genes are shown as boxes above
each map and the translocation breakpoint distributions are shown as line segments below the map of the wild-type genes.
(from exon 13 onward) and the type 2 fusion transcript
consists of the first seven PAX3 exons fused to the last
ten NCOA1 exons (from exon 12 onward).
References
Barr FG. Gene fusions involving PAX and FOX family
members in alveolar rhabdomyosarcoma. Oncogene. 2001
Sep 10;20(40):5736-46
Fusion Protein
Description
The type 1 fusion gene encodes a 894 amino acid
fusion protein and the type 2 fusion gene encodes a
1026 amino acid fusion protein. The fusion proteins
encode novel transcription factors with the PAX3 DNA
binding domain and the NCOA1 transcriptional
activation domains.
Oncogenesis
Transcription dysregulation. At the cellular level there
is evidence of alterations in control of growth, resulting
in transformation of recipient cells (NIH3T3) in
culture.
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(4)
Xu J, Li Q. Review of the in vivo functions of the p160 steroid
receptor
coactivator
family.
Mol
Endocrinol.
2003
Sep;17(9):1681-92
Wachtel M, Dettling M, Koscielniak E, Stegmaier S, Treuner J,
Simon-Klingenstein K, Bühlmann P, Niggli FK, Schäfer BW.
Gene expression signatures identify rhabdomyosarcoma
subtypes and detect a novel t(2;2)(q35;p23) translocation
fusing PAX3 to NCOA1. Cancer Res. 2004 Aug
15;64(16):5539-45
Nishio J, Althof PA, Bailey JM, Zhou M, Neff JR, Barr FG,
Parham DM, Teot L, Qualman SJ, Bridge JA. Use of a novel
FISH assay on paraffin-embedded tissues as an adjunct to
diagnosis of alveolar rhabdomyosarcoma. Lab Invest. 2006
Jun;86(6):547-56
386
Soft tissue tumors: t(2;2)(p23;q35) in alveolar rhabdomyosarcoma
Barr FG
Buckingham M, Relaix F. The role of Pax genes in the
development of tissues and organs: Pax3 and Pax7 regulate
muscle progenitor cell functions. Annu Rev Cell Dev Biol.
2007;23:645-73
transcriptional coactivator family.
Cancer. 2010 Mar;49(3):224-36
Chromosomes
Williamson D, Missiaglia E, de Reyniès A, Pierron G, Thuille B,
Palenzuela G, Thway K, Orbach D, Laé M, Fréneaux P,
Pritchard-Jones K, Oberlin O, Shipley J, Delattre O. Fusion
gene-negative alveolar rhabdomyosarcoma is clinically and
molecularly
indistinguishable
from
embryonal
rhabdomyosarcoma. J Clin Oncol. 2010 May 1;28(13):2151-8
Mercado GE, Barr FG. Fusions involving PAX and FOX genes
in the molecular pathogenesis of alveolar rhabdomyosarcoma:
recent advances. Curr Mol Med. 2007 Feb;7(1):47-61
Xu J, Wu RC, O'Malley BW. Normal and cancer-related
functions of the p160 steroid receptor co-activator (SRC)
family. Nat Rev Cancer. 2009 Sep;9(9):615-30
This article should be referenced as such:
Barr FG. Soft tissue tumors: t(2;2)(p23;q35) in alveolar
rhabdomyosarcoma. Atlas Genet Cytogenet Oncol Haematol.
2011; 15(4):385-387.
Sumegi J, Streblow R, Frayer RW, Dal Cin P, Rosenberg A,
Meloni-Ehrig A, Bridge JA. Recurrent t(2;2) and t(2;8)
translocations in rhabdomyosarcoma without the canonical
PAX-FOXO1 fuse PAX3 to members of the nuclear receptor
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(4)
Genes
387