PMID- 21602886
OWN - NLM
STAT- MEDLINE
DCOM- 20120104
LR  - 20201113
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 30
IP  - 43
DP  - 2011 Oct 27
TI  - Uncommitted precursor cells might contribute to increased incidence of embryonal 
      rhabdomyosarcoma in heterozygous Patched1-mutant mice.
PG  - 4428-36
LID - 10.1038/onc.2011.157 [doi]
AB  - Embryonal rhabdomyosarcoma (ERMS) is a tumor of the skeletal muscle in children 
      and is frequently initiated by heterozygous germline mutations in the Hedgehog 
      (Hh) receptor Patched1 (Ptch), both in humans and mice. Using a conditional 
      knock-out strategy in Ptch(flox/+) mice, we demonstrate that early embryonic 
      stages are more susceptible to ERMS development than later stages and that cells 
      normally not committed to undergo myogenesis at this stage represent the major 
      source of ERMS. We found that deletion of a single copy of the Ptch allele at 
      E9.5 using the ubiquitously active Rosa26CreERT2 resulted in a tumor incidence of 
      88% but reached only 44% and 12% when the Ptch allele was inactivated at E11.5 
      and E13.5, respectively. Induction of the Ptch mutation at E9.5 did also 
      significantly shorten ERMS-free survival and increased tumor multiplicity 
      compared with tumor induction at E11.5 and E13.5. Interestingly, we observed a 
      more that 10-fold reduction of ERMS incidence when the Ptch mutation was 
      specifically introduced in Myf5-expressing cells, which is the myogenic factor 
      expressed in all muscle cells at E9.5. We conclude that Myf5-negative cells are 
      more susceptible to ERMS development than Myf5-positive embryonic precursors. As 
      the propensity to undergo tumorigenic transformation declined with age, 
      concomitant with the increase of stably committed muscle cells, it seems likely 
      that the Ptch mutation favors tumor formation in progenitor cells, which have not 
      yet acquired a muscle cell fate.
FAU - Nitzki, F
AU  - Nitzki F
AD  - Department of Human Genetics, Universitatsmedizin Gottingen, Gottingen, Germany.
FAU - Zibat, A
AU  - Zibat A
FAU - Frommhold, A
AU  - Frommhold A
FAU - Schneider, A
AU  - Schneider A
FAU - Schulz-Schaeffer, W
AU  - Schulz-Schaeffer W
FAU - Braun, T
AU  - Braun T
FAU - Hahn, H
AU  - Hahn H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110523
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Myf5 protein, mouse)
RN  - 0 (Myogenic Regulatory Factor 5)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Ptch1 protein, mouse)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Animals
MH  - Embryonic Development
MH  - Gene Knockout Techniques
MH  - Heterozygote
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mutation
MH  - Myogenic Regulatory Factor 5/*metabolism
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Receptors, Cell Surface/*genetics/physiology
MH  - Rhabdomyosarcoma, Embryonal/*embryology/pathology
MH  - Stem Cells/*physiology
MH  - Time Factors
EDAT- 2011/05/24 06:00
MHDA- 2012/01/05 06:00
CRDT- 2011/05/24 06:00
PHST- 2011/05/24 06:00 [entrez]
PHST- 2011/05/24 06:00 [pubmed]
PHST- 2012/01/05 06:00 [medline]
AID - onc2011157 [pii]
AID - 10.1038/onc.2011.157 [doi]
PST - ppublish
SO  - Oncogene. 2011 Oct 27;30(43):4428-36. doi: 10.1038/onc.2011.157. Epub 2011 May 
      23.