Writing the Book on Environmental Health

Background: Rhabdomyosarcoma is a common malignancy in children. There are two major types of rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion. Result: Totally 17 cases of rhabdomyosarcoma specimens were studied by immunohistochemical or immunofluorescent staining with ATM antibody and revealed that 7 of the 17 cases were negative for ATM expression (41%). Further analyses of rhabdomyosarcoma cell lines with RT-PCR revealed that in Rh30 cells, an alveolar rhabdomyosarcoma cell line, there are three separate deletions/mutations of the ATM mRNA. Western blotting analysis of the Rh30 cellular extract with anti-ATM antibody showed that there is an aberrant form of ATM protein within the Rh30 cells that are smaller than normal control. Conclusion: These results suggest a link of ATM gene deletion/mutation with rhabdomyosarcoma, and since ATM kinase is a crucial regulatory protein in DNA damage repair signaling pathway, and ATM deletion/mutation may contribute to pathogenesis of rhabdomyosarcoma. Background Rhabdomyosarcoma is a malignant neoplasm of skeletal muscle, and is one of the most common soft tissue malignancies in the children and adolescent population. Histopathologically rhabdomyosarcoma can be divided into two major subtypes, embryonal rhabdomyosarcoma representing about 80% of the clinical cases, and alveolar rhabdomyosarcoma representing about 20% of the total cases [1,2]. Extensive cytogenetic studies showed that the embryonal rhabdomyosarcomas are generally associated Published: 3 January 2003 Molecular Cancer 2003, 2:2 Received: 15 December 2002 Accepted: 3 January 2003 This article is available from: http://www.molecular-cancer.com/content/2/1/2 © 2003 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.