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Soft Tissues: Alveolar rhabdomyosarcoma with t(2;2)(p23;q35) PAX3/NCOA1

Written2010-07Frederic G Barr
Department of Pathology, Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

(Note : for Links provided by Atlas : click)


ICD-Topo C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 8920/3 Alveolar rhabdomyosarcoma
Atlas_Id 5445
Phylum Soft Tissues::Alveolar rhabdomyosarcoma
WHO/OMS Classification Soft Tissues

Clinics and Pathology

Phenotype / cell stem origin Alveolar rhabdomyosarcoma (ARMS).
Epidemiology Occurs in a small subset of ARMS cases (<5%). There are five reported cases.
Pathology No information available.


Of the five reported cases, cytogenetics was only performed on one case and demonstrated a normal karyotype.
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 PAX3-NCOA1 fusion-specific RT-PCR assay.

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.
Gene NameNCOA1 (nuclear receptor coactivator 1)
Location 2p23.3
Protein Nuclear receptor transcriptional coactivator - p160 family.

Gene NamePAX3 (paired box gene 3 (Waardenburg syndrome 1))
Location 2q36.1
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.

Result of the chromosomal anomaly

Hybrid Gene
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.
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 (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).
Fusion Protein
Description Comparison of wild-type and fusion products associated with the 2;2 translocation in ARMS. Conserved domains are indicated as open boxes, and functional domains are shown as solid bars. The vertical dash line indicates the translocation fusion points in the type 1 (black) and type 2 (red) fusions. Abbreviations: PB, paired box; HD, homeodomain; bHLH/PAS, basic helix-loop-helix/Per/ARNT/Sim homologous domain; LXXLL, typical LXXLL alpha-helix motifs; HAT, histone acetyltransferase (NCOA1 map adapted from Xu & Li, 2003).
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.


Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma.
Barr FG.
Oncogene. 2001 Sep 10;20(40):5736-46. (REVIEW)
PMID 11607823
The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions.
Buckingham M, Relaix F.
Annu Rev Cell Dev Biol. 2007;23:645-73. (REVIEW)
PMID 17506689
Fusions involving PAX and FOX genes in the molecular pathogenesis of alveolar rhabdomyosarcoma: recent advances.
Mercado GE, Barr FG.
Curr Mol Med. 2007 Feb;7(1):47-61. (REVIEW)
PMID 17311532
Use of a novel FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma.
Nishio J, Althof PA, Bailey JM, Zhou M, Neff JR, Barr FG, Parham DM, Teot L, Qualman SJ, Bridge JA.
Lab Invest. 2006 Jun;86(6):547-56.
PMID 16607381
Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family.
Sumegi J, Streblow R, Frayer RW, Dal Cin P, Rosenberg A, Meloni-Ehrig A, Bridge JA.
Genes Chromosomes Cancer. 2010 Mar;49(3):224-36.
PMID 19953635
Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1.
Wachtel M, Dettling M, Koscielniak E, Stegmaier S, Treuner J, Simon-Klingenstein K, Buhlmann P, Niggli FK, Schafer BW.
Cancer Res. 2004 Aug 15;64(16):5539-45.
PMID 15313887
Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma.
Williamson D, Missiaglia E, de Reynies A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Lae M, Freneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O.
J Clin Oncol. 2010 May 1;28(13):2151-8. Epub 2010 Mar 29.
PMID 20351326
Review of the in vivo functions of the p160 steroid receptor coactivator family.
Xu J, Li Q.
Mol Endocrinol. 2003 Sep;17(9):1681-92. Epub 2003 Jun 12. (REVIEW)
PMID 12805412
Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family.
Xu J, Wu RC, O'Malley BW.
Nat Rev Cancer. 2009 Sep;9(9):615-30. (REVIEW)
PMID 19701241


This paper 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.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(2;2)(p23;q36) PAX3/NCOA1

External links

Mitelman database t(2;2)(p23;q36) [CaseList]     t(2;2)(p23;q36) [Transloc - MCList]   PAX3/NCOA1 Fusion - MCList]
COSMIC[ PAX3 ]   [ NCOA1 ]
arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionPAX3 (2q36.1) NCOA1 (2p23.3)    [fusion1042] [fusion1043] [fusion289] [fusion290]
Mitelman databasePAX3/NCOA1[MCList]    PAX3 (2q36.1) NCOA1 (2p23.3)   t(2;2)(p23;q36)
TICdbPAX3/NCOA1    PAX3 (2q36.1) NCOA1 (2p23.3)
Disease databaseSoft Tissues: Alveolar rhabdomyosarcoma with t(2;2)(p23;q35) PAX3/NCOA1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

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