Genetic mapping of a Ptch1-associated rhabdomyosarcoma susceptibility locus on mouse chromosome 2. Academic Article uri icon

abstract

  • Mutations in the Patched (Ptch1) gene are responsible for various familial and sporadic cancers. Ptch1(neo67/+) mice, in which exons 6 and 7 are deleted, show genetic background-dependent susceptibility to the development of muscle tumors resembling human rhabdomyosarcoma (RMS); BALB/c (BALB) is a susceptible strain whereas C57BL/6 (B6) shows resistance. A genome-wide linkage analysis was carried out using Ptch1(neo67/+)mice produced from B6 x (BALB x B6) backcrosses to identify loci involved in the control of RMS susceptibility. Quantitative trait locus mapping with the censored tumor latency time as the quantitative parameter was used to detect a significant RMS susceptibility modifier locus, Parms1 (Patched-Associated RMS 1), on chromosome 2 between D2Mit37 and D2Mit102 (LRS = 10). A Kaplan-Meier survival curve revealed that mice with the B6/BALB genotype develop tumors more frequently and much faster as compared to mice homozygous for the B6 allele (P = 0.02). Additional loci not reaching linkage significance were also detected for medulloblastoma resistance.

published proceedings

  • Genomics

author list (cited authors)

  • Hahn, H., Nitzki, F., Schorban, T., Hemmerlein, B., Threadgill, D., & Rosemann, M.

citation count

  • 24

complete list of authors

  • Hahn, Heidi||Nitzki, Frauke||Schorban, Tatjana||Hemmerlein, Bernhard||Threadgill, David||Rosemann, Michael

publication date

  • November 2004