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Updated: Jan 25, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
Gain-of-Function Mutations: An Emerging Advantage for Cancer Biology
Yongsheng Li1, Yunpeng Zhang2, Xia Li3
1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA.
Abstract:
Advances in next-generation sequencing have identified thousands of genomic variants that perturb the normal functions of proteins, further contributing to diverse phenotypic consequences in cancer. Elucidating the functional pathways altered by loss-of-function (LOF) or gain-of-function (GOF) mutations will be crucial for prioritizing cancer-causing variants and their resultant therapeutic liabilities. In this review, we highlight the fundamental function of GOF mutations and discuss the potential mechanistic effects in the context of signaling networks. We also summarize advances in experimental and computational resources, which will dramatically help with studies on the functional and phenotypic consequences of mutations. Together, systematic investigations of the function of GOF mutations will provide an important missing piece for cancer biology and precision therapy.
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