Cancer Report

Cancer : Soft tissue tumors: Rhabdomyosarcoma
Cancer Name Soft tissue tumors: Rhabdomyosarcoma
Description Rhabdomyosarcoma (RMS) are mesenchymal tumours belonging to the group of small round-cell tumors, displaying various degrees of striated muscular differentiation t(2;13)(q35;q14) ) G-banding (above) - Courtesy G. Reza Hafez, Eric B.Johnson, and Sara Morrison-Delap, Cytogenetics at the Waisman Center ; R- banding (below) - Courtesy Jean-Luc Lai rhabdomyosarcoma covers two distinct entities:
  • embryonal rhabdosarcoma (E-RMS)
  • alveolar rhabdomyosarcoma (A-RMS)
    Clinics and Pathology
    Epidemiology the most common pediatric soft tissue sarcoma (5 to 8% of all malignancies in childhood): annual incidence is 4/106; E-RMS accounts for 75% of all RMS, and is observed in young children (3-12 yrs); A-RMS is found in the remaining 25 %, and is observed in older children and young adults (6-21 yrs)
  • in E-RMS, tumor cells are round or spindle-shaped and may exhibit various degrees of muscular differentiation; they are often dispersed in an abundant myxoid stroma; the botryoid type, observed in tumors developped in mucosa-lined organs (vagina, bladder), exhibits a polypoid grape-like pattern.
  • in A-RMS, tumor cells are round and more dense than in E-RMS and, typically, they are arranged according a pattern reminiscent of lung alveoli.
  • Prognosis dependent on the extent of disease at time of diagnosis, and on the type of RMS; patients with A-RMS have a poorer survival than those with E-RMS
    Related Genes
    Gene Symbol HRAS
    Description From COSMIC:
    Gene Symbol TOPORS
    Description From COSMIC:
    Gene Symbol PAX3
    Description From cancer gene census of CGP:
    Gene Symbol N-RAS
    Description From COSMIC:
    Gene Symbol BUB1B
    Description From cancer gene census of CGP:
    Gene Symbol CDKN2A
    Description From COSMIC:
    Gene Symbol K-RAS
    Description From COSMIC:
    Gene Symbol SIX1
    Description From OMIM: "Yu et al. (2004) established highly and poorly metastatic rhabdomyosarcoma cell lines derived from a transgenic mouse model overexpressing Hgf/Sf (142409) and deficient for Ink4a/Arf (600160), in which skeletal muscle tumors reminiscent of those in embryonic rhabdomyosarcoma (268210) arise with very high penetrance and short latency (Sharp et al., 2002). Yu et al. (2004) then used cDNA microarray analysis of these cell lines to identify a set of genes whose expression was significantly different between highly and poorly metastatic cells. Subsequent in vivo functional studies revealed that ezrin, encoded by Vil2 (123900), and Six1 have essential roles in determining the metastatic fate of rhabdomyosarcoma cells. VIL2 and SIX1 expression was enhanced in human rhabdomyosarcoma tissue, significantly correlating with clinical stage"
    Gene Symbol SMARCB1
    Description From COSMIC:
    Gene Symbol DDX43
    Description From OMIM: "To identify genes with tumor-specific expression, Martelange et al. (2000) applied a cDNA subtraction approach, i.e., representational difference analysis, to a human rhabdomyosarcoma cell line. They obtained 2 cDNAs that appeared to be tumor specific and named the corresponding genes SAGE and HAGE because they had the same pattern of expression as genes of the MAGE family (e.g., MAGEA1; 300016). The putative HAGE protein contains 648 amino acids and is a member of the DEAD box family of ATP-dependent RNA helicases (see 600396). Northern blot analysis detected expression of a 2.2-kb HAGE transcript in tumors of various histologic types at a level that was 100-fold higher than that observed in normal tissues, except for testis. "
    Gene Symbol FOXO1A
    Description From cancer gene census of CGP:
    Gene Symbol PTPN11
    Description From COSMIC:
    Gene Symbol SMO
    Description From OMIM: "Basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, and other human tumors are associated with mutations that activate the protooncogene 'Smoothened' or that inactivate the tumor suppressor 'Patched.' Smoothened and Patched mediate the cellular response to the Hedgehog secreted protein signal, and oncogenic mutations affecting these proteins cause excess activity of the Hedgehog response pathway. Taipale et al. (2000) showed that the plant-derived teratogen cyclopamine, which inhibits the Hedgehog response, is a potential mechanism-based therapeutic agent for treatment of these tumors."
    Gene Symbol PAX7
    Description From cancer gene census of CGP, OMIM
    Gene Symbol NBS1
    Description From cancer gene census of CGP:
    Gene Symbol BRAF
    Description From COSMIC:
    Cytogenetics Morphological
  • E-RMS do not show recurrent structural chromosome rearrangement; the majority of the tumors are hyperdiploid, with an increased copy number for chromosomes 2, 7, 8, 12, and 13, in particular; comparative genomic hybridization (CGH) confirms these findings, showing gains of a variety of whole chromosomes, 2, 13, 12, 8, and 7 (in 50-60% of the cases), 17, 18, and 19 (40%), and the loss of chromosomes 16 and 10 (in 30-40%), and 15 and 14 (20%); polymorphism studies shows that E-RMS is associated with the loss of heterozygosity at 11p13.
  • A-RMS is characterized by two pathognomonic translocations:
    - t(2;13)(q35;q14) and
    - t(1;13)(p36;q14), found in 80 and 15% of the cases respectively,
    leading to the formation of gene fusions, namely
    - PAX3 - FKHR, in the t(2;13), and
    - PAX7 - FKHR in the t(1;13), generating fusion transcripts;
    double-minute chromosomes have been reported in some RMS, and CGH has showed a high frequency of genomic amplifications; the amplicons are located in 12q13-15 (50% of the cases), 2p24 (36%), 13q14, 13q32, and 1q36 (14%), 1q21 and 8q13-q21 (7%);
    the 12q13-15 amplicon could involve genes:
    - CHOP,
    - MDM2, and
    - SAS;
    - MYCN gene is amplified in cases with the amplicon at 2p24, but unlike in neuroblastoma, no correlation with prognosis seems to exist in RMS; cases with the fusion PAX7-FKHR often show an amplification of the fusion gene (and more frequently than cases with the PAX3-FKHR gene do).
    Title Cytogenetic studies in subgroups of rhabdomyosarcoma.
    Authors "Whang-Peng, J.; Knutsen, T.; Theil, K.; Horowitz, M. E.; Triche, T. "
    Citations "Genes Chromosomes Cancer 5: 299-310, 1992. "
    PubMedID 1283318
    Title A new highly polymorphic DNA restriction site marker in the 5' region o the human tyrosine hydroxylase gene (TH) detecting loss of heterozygosity in human embryonal rhabdomyosarcoma.
    Authors Besnard-Guerin C, Cavenee WK, Newsham I
    Citations Hum Genet. 1994 Mar;93(3):349-50
    PubMedID 94171243
    Title Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas. Report of an international study of four pathology classifications.
    Authors Asmar L, Gehan EA, Newton WA, Webber BL, Marsden HB, van Unnik AJ, Hamoudi AB, Shimada H, Tsokos M, Harms D, et al
    Citations Cancer. 1994 Nov 1;74(9):2579-88
    PubMedID 95007400
    Title Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma
    Authors Davis RJ, D'Cruz CM, Lovell MA, Biegel JA, Barr FG
    Citations Cancer Res. 1994 Jun 1;54(11):2869-72.
    PubMedID 94243800
    Title Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine.
    Authors "Taipale, J.; Chen, J. K.; Cooper, M. K.; Wang, B.; Mann, R. K.; Milenkovic, L.; Scott, M. P.; Beachy, P. A."
    Citations "Nature 406: 1005-1009, 2000."
    PubMedID 10984056
    Title Identification on a human sarcoma of two new genes with tumor-specific expression.
    Authors Martelange, V.; De Smet, C.; De Plaen, E.; Lurquin, C.; Boon, T. :
    Citations Cancer Res. 60: 3848-3855, 2000.
    PubMedID 10919659
    Title The molecular pathology of small round-cell tumours--relevance to diagnosis, prognosis, and classification
    Authors McManus AP, Gusterson BA, Pinkerton CR, Shipley JM
    Citations J Pathol. 1996 Feb;178(2):116-21. Review.
    PubMedID 96246664
    Title Novel formation and amplification of the PAX7-FKHR fusion gene in a case of alveolar rhabdomyosarcoma.
    Authors Weber-Hall S, McManus A, Anderson J, Nojima T, Abe S, Pritchard-Jones K, Shipley J
    Citations Genes Chromosomes Cancer. 1996 Sep;17(1):7-13
    PubMedID 97044430
    Title Gains, losses, and amplification of genomic material in rhabdomyosarcoma analyzed by comparative genomic hybridization.
    Authors Weber-Hall S, Anderson J, McManus A, Abe S, Nojima T, Pinkerton R, Pritchard-Jones K, Shipley J
    Citations Cancer Res. 1996 Jul 15;56(14):3220-4
    PubMedID 96320461
    Title Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma.
    Authors Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher FJ 3d, Emanuel BS, Rovera G, Barr FG
    Citations Nat Genet. 1993 Nov;5(3):230-5
    PubMedID 94100975
    Title MYCN gene amplification in rhabdomyosarcoma.
    Authors Driman D, Thorner PS, Greenberg ML, Chilton-MacNeill S, Squire J
    Citations Cancer. 1994 Apr 15;73(8):2231-7
    PubMedID 94207987
    Title MDM2 amplification in a primary alveolar rhabdomyosarcoma displaying a t(2;13)(q35;q14).
    Authors Meddeb M, Valent A, Danglot G, Nguyen VC, Duverger A, Fouquet F, Terrier-Lacombe MJ, Oberlin O, Bernheim A
    Citations Cytogenet Cell Genet. 1996;73(4):325-30
    PubMedID 96354860
    Title Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators.
    Authors "Yu, Y.; Khan, J.; Khanna, C.; Helman, L.; Meltzer, P. S.; Merlino, G."
    Citations "Nature Med. 10: 175-181, 2004."
    PubMedID 14704789
    Source and Citation
    Source Atlas of Genetics and Cytogenetics in Oncology and Haematology
    Citation Couturier J . Soft tissue tumors: Rhabdomyosarcoma. Atlas Genet Cytogenet Oncol Haematol. March 1998 .
    URL :