Molecular Characterization of Patched-associated Rhabdomyosarcoma by Conditional Gene Targeting

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390319
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: HAYASHI Yutaka Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (40125638)
• Co-Investigator(Kenkyū-buntansha): NODA Tetsuo The cancer institute of Japanese Foundation For Cancer Research, A deputy chief, 癌研究所, 副所長 (10183550)
• Project Period (FY): 2003 – 2005
• Keywords: Rhabdomyosarcoma / Patched / Nevoid Basal Cell Carcinoma Syndrome / Sonic hedge hog signal / conditional gene targeting / muscle specific Ptc1 knockout mouse

Research Abstract

Gorlin syndrome, which is an autosomal dominant disorder characterized by a combination of developmental defects with a predisposition to tumor formation, is cause by germline mutations of the human homolog of the drosophila segment polarity gene patched (PTCH). The Ptch1 mutant mice spontaneously develop rhabdomyosarcoma (RMS) dependent on the genetic background. The mutant mice on CD-1 background, but not C57BL/6 one, were sensitive to RMS. The downstream signaling partner of Ptch1,Gli1 was overexpressed in all RMSs analyzed, indicating that abnormal Sonic Hedgehog/Patched (Shh) signaling pathway should be common for the various tumors associated with this syndrome. Insulin-like growth factor 2 (Igf2) was also overexpressed, suggesting cross-talk between Shh and Igf2 pathways in tumorigenesis. However, the genetic and molecular lesions of RMS underlying its genesis and progression remain largely unknown. In this study we have compared the molecular profiles of RMS versus normal skeletal muscle by RT-PCR, real time PCR analysis. Our results provide a first step towards a molecular classification of RMS.