Quaking but not parkin is the major tumor suppressor in 6q deleted region in glioblastoma

Fatma Betul Aksoy Yasar; Takashi Shingu; Daniel B Zamler; Mohammad Fayyad Zaman; Derek Lin Chien; Qiang Zhang; Jiangong Ren; Jian Hu

doi:10.3389/fcell.2022.931387

Quaking but not parkin is the major tumor suppressor in 6q deleted region in glioblastoma

Front Cell Dev Biol. 2022 Aug 16:10:931387. doi: 10.3389/fcell.2022.931387. eCollection 2022.

Authors

Fatma Betul Aksoy Yasar^{1

2}, Takashi Shingu¹, Daniel B Zamler^{1

2

3}, Mohammad Fayyad Zaman², Derek Lin Chien⁴, Qiang Zhang¹, Jiangong Ren⁵, Jian Hu^{1

2}

Affiliations

¹ Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
² The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, United States.
³ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
⁴ School of Arts and Sciences, University of Rochester, Rochester, NY, United States.
⁵ Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Abstract

Glioblastoma (GBM) is a high-grade, aggressive brain tumor with dismal median survival time of 15 months. Chromosome 6q (Ch6q) is a hotspot of genomic alterations, which is commonly deleted or hyper-methylated in GBM. Two neighboring genes in this region, QKI and PRKN have been appointed as tumor suppressors in GBM. While a genetically modified mouse model (GEMM) of GBM has been successfully generated with Qk deletion in the central nervous system (CNS), in vivo genetic evidence supporting the tumor suppressor function of Prkn has not been established. In the present study, we generated a mouse model with Prkn-null allele and conditional Trp53 and Pten deletions in the neural stem cells (NSCs) and compared the tumorigenicity of this model to our previous GBM model with Qk deletion within the same system. We find that Qk but not Prkn is the potent tumor suppressor in the frequently altered Ch6q region in GBM.

Keywords: GBM; QKI; glioblastoma; glioma; parkin.