Soft tissue sarcomas account for up to 8 % of all childhood cancers and 2 % of childhood cancer deaths, with an incidence of about 8 per 1,000,000 per year. About half occur in children aged under 3 years, with an equal sex incidence. Rhabdomyosarcoma accounts for two-thirds of pediatric soft tissue sarcomas (McDowell 2003) and most commonly arise in the head and neck (40 %), genitourinary tract (20 %), and extremities (20 %) (Crist and Kun 1991). On histological criteria, rhabdomyosarcoma may be classified into two main subtypes: embryonal and botryoid (two-thirds of all Tumours) and alveolar (one-third).
Most rhabdomyosarcomas are sporadic, but they complicate neurofibromatosis type 1 (Brems et al. 2009), the Beckwith– Wiedemann syndrome (Lapunzina 2005), and the Li–Fraumeni syndrome. Segregation analysis for soft tissue sarcomas in the absence of a known genetic syndrome suggests a heritability of 0.13, due to a postulated rare autosomal dominant gene (population frequency 0.00002) with a penetrance of 50 and 90 % at ages 30 and 60 years, respectively. The risk to first-degree relatives is significantly increased if the index case has two or more primaries (Burke et al. 1991).
Germline mutations in TP53 may be detected in around 10 % of children with rhabdomyosarcoma (Diller et al. 1995), especially orbital alveolar rhabdomyosarcomas, and rhabdomyosarcoma is the second most prevalent Tumours in Li–Fraumeni syndrome after breast cancer (Olivier et al. 2003).
Embryonal rhabdomyosarcoma (which occurs in 6 % of Tumours in Beckwith– Wiedemann syndrome) specifically shows chromosome 11p allele loss in the same region as the Beckwith–Wiedemann gene. A translocation between chromosomes 2 and 13, (2; 13)(q37; q14), has been described specifically in rhabdomyosarcoma (Meddeb et al. 1996); although it is most frequent in alveolar rhabdomyosarcoma, it has also been reported in embryonal and undifferentiated types. Embryonal rhabdomyosarcomas are the most common Tumours associated with Costello syndrome (Gripp 2005), and they may also be seen in children with any of the “RASopathies” (i.e., with germline mutations in genes which are part of the Ras/mitogen-activated protein kinase (MAPK) pathway), including Noonan, LEOPARD, and cardio-cutaneous-facial syndromes (Tidyman and Rauen 2009; Denayer et al. 2010). They also have been described in individuals with biallelic PMS2 mutations (Kratz et al. 2009) and in Nijmegen breakage syndrome (Meyer and Spunt 2004) embryonal rhabdomyosarcomas are also reported in DICER1 mutation carriers, particularly those arising from the cervix (Foulkes et al. 2011).