Chromosomal and Genetic Imbalances in Chinese Patients with Rhabdomyosarcoma Detected by High-resolution Array Comparative Genomic Hybridization

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. Although associations between ARMS tumorigenesis and PAX3, PAX7, and FKHR are well recognized, the complete genetic etiology underlying RMS pathogenesis and progression remains unclear. Chromosomal copy number variations (CNVs) and the involved genes may play important roles in the pathogenesis and progression of human malignancies. Using high-resolution array comparative genomic hybridization (aCGH), we examined 20 formalin-fixed, paraffin-embedded (FFPE) RMS tumors to explore the involvement of the relevant chromosomal regions with resident genes in RMS tumorigenesis. In RMS, frequent gains were identified on chromosome regions 12q13.3-q14.1, 12q24.31, 17q25.1, 1q21.1, and 7q11.23, whereas frequent losses were observed on chromosome regions 5q13.2, 14q32.33, and 15q11.2. Amplifications were observed on chromosome regions 9p13.3, 12q13.3-q14.1, 12q15, and 16p13.11, whereas deletions were detected on chromosome regions 1p36.33, 1p13.1, 2q11.1, 5q13.2, 8p23.1, 9p24.3, and 16p11.2. Frequent gains were detected in GLI1, GEFT, OS9, and CDK4 (12q13.3-q14.1), being 60% in embryonal rhabdomyosarcoma (ERMS) and 66.67% in alveolar rhabdomyosarcoma (ARMS), respectively. However, frequent losses were detected in IGHG1, IGHM, IGHG3, and IGHG4 (14q32.33), being 70% in ERMS and 55.56% in and ARMS, respectively. Frequent gains were detected in TYROBP, HCST, LRFN3, and ALKBH6 (19q13.12) in ERMS but not in ARMS. The frequency of TYROBP, HCST, LRFN3, and ALKBH6 gains is significantly different in ERMS versus ARMS (P=0.011). The results suggest that novel TYROBP, HCST, LRFN3, and ALKBH6 genes may play important roles in ERMS. The technique used is a feasible approach for array comparative genomic hybridization analysis in archival tumor samples.