Wilms tumor 1
The Wilms tumor 1 (WT1) gene is a critical gene associated with the development of Wilms tumor, a type of kidney cancer that primarily affects children.
WT1 is highly expressed in many solid tumors (such as ovarian, breast, lung, and colorectal cancers) as well as hematologic malignancies (e.g., acute leukemias).
WT1 is generally overexpressed in many cancers and is associated with aggressive tumor behavior and poorer prognosis in several contexts. Its multifunctional nature, marked by its ability to act as both a transcriptional activator and repressor, underlies its complex role in tumorigenesis.
Direction of Regulation in Cancer
WT1 shows two dominant, context-dependent directions:
A. Loss-of-function (Downregulated activity) — Tumor suppressor role
-Classic in Wilms tumor (pediatric kidney cancer)
-Inactivating mutations or loss reduce differentiation control
-Leads to aberrant developmental programs and tumorigenesis
B. Overexpression (Functionally upregulated) — Oncogenic support
-Common in hematologic malignancies (AML, MDS) and several solid tumors
-WT1 is overexpressed without mutation
-Supports survival, proliferation, and stem-like states
Thus, WT1 is not unidirectional: it is a tumor suppressor in some tissues and an oncogenic enabler in others.
WT1 as a Biomarker (Major Clinical Use)
-Disease burden marker in leukemia: WT1 mRNA levels are widely used to monitor minimal residual disease (MRD).
-High WT1 expression → higher relapse risk.
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