Novel PDGFRB rearrangement in multifocal infantile myofibromatosis is tumorigenic and sensitive to imatinib

Mohammed Hassan, Erin Butler, Raphael Wilson, Angshumoy Roy, Yanbin Zheng, Priscilla Liem, Dinesh Rakheja, Dean Pavlick, Lauren L. Young, Mark Rosenzweig, Rachel Erlich, Siraj M. Ali, Patrick J. Leavey, D. Williams Parsons, Stephen X. Skapek, Theodore W. Laetsch

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Infantile myofibromatosis (IM) is an aggressive neoplasm composed of myofibroblast-like cells in children. Although typically localized, it can also present as multifocal disease, which represents a challenge for effective treatment. IM has previously been linked to activating somatic and germline point mutations in the PDGFRβ tyrosine kinase encoded by the PDGFRB gene. Clinical panel-based targeted tumor sequencing of a tumor from a newborn with multifocal IM revealed a novel PDGFRB rearrangement, which was reported as being of unclear significance. Additional sequencing of cDNA from tumor and germline DNA confirmed a complex somatic/mosaic PDGFRB rearrangement with an apparent partial tandem duplication disrupting the juxtamembrane domain. Ectopic expression of cDNA encoding the mutant form of PDGFRB markedly enhanced cell proliferation of mouse embryo fibroblasts (MEFs) compared to wild-type PDGFRB and conferred tumor-forming capacity on nontumorigenic 10T1/2 fibroblasts. The mutated protein enhanced MAPK activation and retained sensitivity to the PDGFRβ inhibitor imatinib. Our findings reveal a new mechanism by which PDGFRB can be activated in IM, suggest that therapy with tyrosine kinase inhibitors including imatinib may be beneficial, and raise the possibility that this receptor tyrosine kinase might be altered in a similar fashion in additional cases that would similarly present annotation challenges in clinical DNA sequencing analysis pipelines.

Original languageEnglish (US)
Article numbera004440
JournalCold Spring Harbor Molecular Case Studies
Issue number5
StatePublished - 2019

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Novel PDGFRB rearrangement in multifocal infantile myofibromatosis is tumorigenic and sensitive to imatinib'. Together they form a unique fingerprint.

Cite this