TRIM28 variants and Wilms' tumour predisposition.

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• * Tripartite motif-containing protein 28 (TRIM28) is a recently identified Wilms' tumour (WT) predisposition gene.
• * Germline pathogenic variants in TRIM28 are found in approximately 1% of isolated and 8% of familial WT cases.
• * TRIM28 functions as a tumour suppressor gene in pediatric WT, with biallelic disruption typically observed in tumour tissue.

Purpose of the Study:

• * To review the inheritance patterns, histopathological, and clinical features of TRIM28-associated WT.
• * To explore potential mechanisms of tumorigenesis in embryonic kidney development linked to TRIM28.
• * To highlight the utility of immunohistochemistry for detecting TRIM28 protein loss in identifying patients with pathogenic variants.

Main Methods:

• * Review of existing literature on TRIM28 and Wilms' tumour.
• * Analysis of inheritance patterns, histopathology, and clinical presentations.
• * Immunohistochemical assessment of TRIM28 protein expression in tumour tissues.

Main Results:

• * TRIM28 variants are associated with epithelial WT, but can occur with other histological subtypes.
• * Loss of TRIM28 protein expression via immunohistochemistry is a reliable indicator of pathogenic TRIM28 variants.
• * Biallelic disruption of TRIM28 is common in pediatric WT cases.

Conclusions:

• * Identifying germline TRIM28 variants in WT patients facilitates genetic counseling and family screening.
• * Further research into TRIM28-associated WT is crucial for understanding tumorigenesis mechanisms.
• * TRIM28 plays a significant role in embryonic kidney development and WT pathogenesis.