Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: A report from the Children's Oncology Group

被引:49
作者
Blandford, MC
Barr, FG
Lynch, JC
Randall, RL
Qualman, SJ
Keller, C
机构
[1] Univ Utah, Dept Pediat, Div Pediat Hematol Oncol, Salt Lake City, UT USA
[2] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[3] Univ Nebraska Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA
[4] Univ Utah, Huntsman Canc Inst, Sarcoma Serv, Dept Orthoped, Salt Lake City, UT USA
[5] Columbus Childrens Hosp, Dept Lab Med, Columbus, OH USA
关键词
insulin-like growth factor; rnetastasis; myogenesis; platelet-derived growth factor; progression; rhabdomyosarcoma;
D O I
10.1002/pbc.20466
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background. Unresectable or metastatic disease represents the greatest obstacle to cure for children with rhabdomyosarcoma. in this study we sought to identify gene expression signatures of advanced stage and progressive disease. Procedure. Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhabdomyosarcoma Study-IV. Results. While the expression profile of rhabdomyosarcomas closely paralleled gene expression profiles of normal embryonic myogenic progenitors, growth factors were most closely associated with disease progression. Specifically, we identified platelet-derived growth factor (PDGF) receptors and insulin-like growth factor as strongly correlated with decreased failure-free survival. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) of an independent data set suggested that autocrine growth signaling, if present, is not regulated in a simple manner at the transcriptional level. Conclusions. increased transcriptional levels of PDGF receptors and insulin-like growth factor are associated with decreased survival in rhabdomyosarcomas. Dual blockade of these growth-factor-signaling pathways may be a valuable strategy in preclinical therapeutic Studies.
引用
收藏
页码:329 / 338
页数:10
相关论文
共 49 条
[1]   The importance of timing differentiation during limb muscle development [J].
Amthor, H ;
Christ, B ;
Weil, M ;
Patel, K .
CURRENT BIOLOGY, 1998, 8 (11) :642-652
[2]   Embryonic expression of the tumor-associated PAX3-FKHR fusion protein interferes with the developmental functions of Pax3 [J].
Anderson, MJ ;
Shelton, GD ;
Cavenee, WK ;
Arden, KC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (04) :1589-1594
[3]   Medical Progress - Common musculoskeletal tumors of childhood and adolescence [J].
Arndt, CAS ;
Crist, WM .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (05) :342-352
[4]   MOLECULAR ASSAYS FOR CHROMOSOMAL TRANSLOCATIONS IN THE DIAGNOSIS OF PEDIATRIC SOFT-TISSUE SARCOMAS [J].
BARR, FG ;
CHATTEN, J ;
DCRUZ, CM ;
WILSON, AE ;
NAUTA, LE ;
NYCUM, LM ;
BIEGEL, JA ;
WORNER, RB .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 273 (07) :553-557
[5]   APPLICATION OF A SIMPLIFIED COMPARATIVE GENOMIC HYBRIDIZATION TECHNIQUE TO SCREEN FOR GENE AMPLIFICATION IN PEDIATRIC SOLID TUMORS [J].
BAYANI, J ;
THORNER, P ;
ZIELENSKA, M ;
PANDITA, A ;
BEATTY, B ;
SQUIRE, JA .
PEDIATRIC PATHOLOGY & LABORATORY MEDICINE, 1995, 15 (06) :831-844
[6]  
Borycki AG, 2000, DEVELOPMENT, V127, P2075
[7]   Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: A report from the Intergroup Rhabdomyosarcoma Study Group [J].
Breitfeld, PP ;
Lyden, E ;
Raney, RB ;
Teot, LA ;
Wharam, M ;
Lobe, T ;
Crist, WM ;
Maurer, HM ;
Donaldson, SS ;
Ruymann, FB .
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 2001, 23 (04) :225-233
[8]   Skeletal muscle formation in vertebrates [J].
Buckingham, M .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2001, 11 (04) :440-448
[9]   The formation of skeletal muscle: from somite to limb [J].
Buckingham, M ;
Bajard, L ;
Chang, T ;
Daubas, P ;
Hadchouel, J ;
Meilhac, S ;
Montarras, D ;
Rocancourt, D ;
Relaix, F .
JOURNAL OF ANATOMY, 2003, 202 (01) :59-68
[10]   Gleevec™ for the treatment of chronic myelogenous leukemia:: US food and drug administration regulatory mechanisms, accelerated approval, and orphan drug status [J].
Cohen, MH ;
Moses, ML ;
Pazdur, R .
ONCOLOGIST, 2002, 7 (05) :390-392