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Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes

Authors

  • Julia A. Bridge,

    Corresponding author
    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
    2. Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska
    3. Department of Orthopedic Surgery, University of Nebraska Medical Center, Omaha, Nebraska
    • Department of Pathology and Microbiology, 983135 Nebraska Medical Center, Omaha, NE 68198
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  • Jian Liu,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
    2. Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska
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  • Stephen J. Qualman,

    1. Department of Laboratory Medicine, Children's Hospital, Columbus, Ohio
    2. Department of Pathology, Ohio State University College of Medicine and Public Health, Columbus, Ohio
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  • Ron Suijkerbuijk,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
    2. Department of Human Genetics, University Hospital, Nijmegen, The Netherlands
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  • Gail Wenger,

    1. Department of Laboratory Medicine, Children's Hospital, Columbus, Ohio
    2. Department of Pathology, Ohio State University College of Medicine and Public Health, Columbus, Ohio
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  • Ji Zhang,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
    2. Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska
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  • Xiaoying Wan,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
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  • K. Scott Baker,

    1. Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
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  • Poul Sorensen,

    1. Department of Pathology, British Columbia's Children's Hospital, Vancouver, Canada
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  • Frederic G. Barr

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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Abstract

In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript–positive and –negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas. © 2002 Wiley-Liss, Inc.

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