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Full transcriptome analysis of rhabdomyosarcoma, normal and fetal skeletal muscle: statistical comparison of multiple SAGE libraries
Author(s) -
Schaaf Gerben J.,
Ruijter Jan M.,
Ruissen Fred,
Zwijnenburg Danny A.,
Waaijer Raymond,
Valentijn Linda J.,
Benit-Deekman Jennifer,
Kampen Antoine H. C.,
Baas Frank,
Kool Marcel
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2104fje
Subject(s) - skeletal muscle , transcriptome , rhabdomyosarcoma , biology , serial analysis of gene expression , gene , gene expression , genetics , bioinformatics , pathology , anatomy , medicine , sarcoma
Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children. Improved treatment strategies have increased overall survival, but the response of approximately one‐third of the patients is still poor. To increase the knowledge of RMS pathogenesis, we performed the first full transcriptome analysis of RMS using serial analysis of gene expression (SAGE). With a G‐test for the simultaneous comparison of subsets of SAGE libraries of normal skeletal muscle, embryonal (ERMS) and alveolar (ARMS) RMS, we identified 251 differentially expressed genes. A literature‐mining procedure demonstrated that 158 of these genes have not previously been associated with RMS or normal muscle. Gene Ontology (GO) analysis assigned 198 of the 251 genes to muscle‐specific classes, including those involved in normal myogenic development, as well as tumor‐related classes. Prominent GO classes were those associated with proliferation and actin reorganization, which are processes that play roles during early muscle development, muscle function, and tumor progression. Using custom microarrays, we confirmed the (up‐ or down‐) regulation of 80% of 98 differentially expressed genes. Another SAGE library of 19‐ to 22‐week‐old fetal skeletal muscle was compared with the RMS and normal muscle transcriptomes. Cluster analysis showed that the RMS and fetal muscle SAGE libraries formed one cluster distinct from normal muscle samples. Moreover, the expression profile of 86% of the differentially expressed genes between normal muscle and RMS was highly similar in fetal muscle and RMS. In conclusion, the G‐test is a robust tool for analyzing groups of SAGE libraries and correctly identifies genes marking the difference between fully differentiated skeletal muscle and RMS. This study not only substantiates the close association between embryonic myogenesis and RMS development but also provides a rich source of candidate genes to further elucidate the etiology of RMS or to identify diagnostic and/or prognostic markers.