دورية أكاديمية
The Landscape of Glycogen synthase kinase-3 beta (GSK-3b) Genomic Alterations in Cancer.
| العنوان: | The Landscape of Glycogen synthase kinase-3 beta (GSK-3b) Genomic Alterations in Cancer. |
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| المؤلفون: | Borden, Brittany A, Baca, Yasmine, Xiu, Joanne, Tavora, Fabio, Winer, Ira, Weinberg, Benjamin A, VanderWalde, Ari M, Darabi, Sourat, Korn, W Michael, Mazar, Andrew P, Giles, Francis J, Crawford, Lorin, Safran, Howard, El-Deiry, Wafik S, Carneiro, Benedito A |
| المصدر: | Articles, Abstracts, and Reports |
| بيانات النشر: | Providence St. Joseph Health Digital Commons |
| سنة النشر: | 2020 |
| المجموعة: | Providence St. Joseph Health Digital Commons |
| مصطلحات موضوعية: | genomics, Genetics and Genomics, Oncology |
| الوصف: | 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. Uterine endometrioid carcinoma was the most commonly mutated (4%) tumor, and copy number variations (CNVs) were most commonly observed in squamous histologies. Significant differences across cancer types for GSK-3B-mutated tumors were observed for B cells (p=0.018), monocytes (p=0.002), dendritic cells (p=0.005), neutrophils (p=0.0003), and endothelial cells(p=0.014). GSK-3B mRNA expression was highest in melanoma. The frequency of PD-L1 expression was higher among GSK-3B-mutated tumors compared to wild-type in colorectal cancer(p=0.03), endometrial cancer(p=0.05), melanoma(p=0.02), ovarian carcinoma(p=0.0001), and uterine sarcoma(p=0.002). Overall, GSK-3B molecular alterations were detected in approximately 1% of solid tumors, tumors with GSK-3B mutations displayed a microenvironment with increased infiltration of B cells, and GSK-3B mutations were associated with increased PD-L1 expression in selected histologies. These results advance the understanding of GSK-3B complex signaling network interfacing with key pathways involved in carcinogenesis and immune response. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.psjhealth.org/publications/3806Test; https://pubmed.ncbi.nlm.nih.gov/33087512Test |
| الإتاحة: | https://digitalcommons.psjhealth.org/publications/3806Test https://pubmed.ncbi.nlm.nih.gov/33087512Test |
| رقم الانضمام: | edsbas.E63DF4CC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |