The Landscape of Glycogen synthase kinase-3 beta (GSK-3b) Genomic Alterations in Cancer


Brittany A Borden, Yasmine Baca, Joanne Xiu, Fabio Tavora, Ira Winer, Benjamin A. Weinberg, Ari M VanderWalde, Sourat Darabi, W. Michael Korn, Andrew P. Mazar, Francis J Giles, Lorin Crawford, Howard Safran, Wafik S. El-Deiry and Benedito A Carneiro


Glycogen synthase kinase-3B (GSK-3B), a serine/threonine kinase, has been implicated in the pathogenesis of many cancers, with involvement in cell cycle regulation, apoptosis, and immune response. Small molecule GSK-3B inhibitors are currently undergoing clinical investigation. Tumor sequencing has revealed genomic alterations in GSK-3B, yet an assessment of the genomic landscape in malignancies is lacking. This study assessed >100,000 tumors from two databases to analyze GSK-3B alterations. GSK-3B expression and immune cell infiltrate data was analyzed across cancer types, and PD-L1 expression was compared between GSK-3B-mutated and wild-type tumors. GSK-3B was mutated at a rate of 1%. The majority of mutated residues were in the kinase domain, with frequent mutations occurring in a GSK-3B substrate binding pocket.

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