The perfect PTEN - transcriptional regulation by PTEN dictates sarcoma identity

Casey G Langdon; Mark E Hatley

doi:10.1080/23723556.2021.2002120

The perfect PTEN - transcriptional regulation by PTEN dictates sarcoma identity

Mol Cell Oncol. 2021 Nov 22;8(6):2002120. doi: 10.1080/23723556.2021.2002120. eCollection 2021.

Authors

Casey G Langdon¹, Mark E Hatley¹

Affiliation

¹ Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Abstract

Fusion-negative rhabdomyosarcoma (FN-RMS) is molecularly heterogeneous with few universal alterations except for Phosphatase and tensin homolog (PTEN) promoter hypermethylation. We demonstrate that losing Pten in FN-RMS engages an aberrant transcriptional program key in tumor maintenance and cell identity. These results highlight the importance between transcriptional state, cell of origin, and genetic perturbation in tumorigenesis.

Keywords: Rhabdomyosarcoma; PTEN; PAX7; DBX1; leiomyosarcoma; mouse models of cancer; core regulatory circuits; Sarcoma ;pediatric cancer; cancer and development.

Grants and funding

This work was supported by the NIH National Cancer Institute grants R01CA216344 (MEH) and R01CA251436 (MEH), the V Foundation for Cancer Research (MEH), and the Rally Foundation for Childhood Cancer Research and Open Hands Overflowing Hearts award number 20IC23 (MEH). This work was also supported by the St. Jude Cancer Center Support Grant (P30CA21765) and American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital.