Rb1 loss modifies but does not initiate alveolar rhabdomyosarcoma.

ABSTRACT:

Background

Alveolar rhabdomyosarcoma (aRMS) is a myogenic childhood sarcoma frequently associated with a translocation-mediated fusion gene, Pax3:Foxo1a.

Methods

We investigated the complementary role of Rb1 loss in aRMS tumor initiation and progression using conditional mouse models.

Results

Rb1 loss was not a necessary and sufficient mutational event for rhabdomyosarcomagenesis, nor a strong cooperative initiating mutation. Instead, Rb1 loss was a modifier of progression and increased anaplasia and pleomorphism. Whereas Pax3:Foxo1a expression was unaltered, biomarkers of aRMS versus embryonal rhabdomyosarcoma were both increased, questioning whether these diagnostic markers are reliable in the context of Rb1 loss. Genome-wide gene expression in Pax3:Foxo1a,Rb1 tumor

SUBMITTER: Kikuchi K 

PROVIDER: S-EPMC4177545 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature