Molecular insight into multiple Wilms tumors arising in germline <i>WT1</i>‐mutated/11p13‐deleted patients

Perotti, Daniela

doi:10.1002/pbc.27360

Cited by 1 publication

(2 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[30][31][32]39 In fact, Scott et al 6 found only germline and no somatic WT1 variants in patients a unique 11p breakpoint on the second allele, suggesting that the "second hit" occurred as an independent genetic event. [42][43][44] Furthermore, unique CTNNB1 variants in each tumor usually follow WT1 variants. 37 A summary of the molecular mechanisms leading to BWT in children with germline WT1 aberrations is shown in Figure 2.…”

Section: Wt1mentioning

confidence: 99%

“…A substantial proportion of WT with WT1 pathogenic variants are associated with pUPD on 11p, encompassing both 11p13 and 11p15.5, which results in biallelic inactivation of WT1 and biallelic expression of IGF2 . Recent studies of BWT and multifocal WT with WT1 pathogenic germline variants, including patients with WAGR, show that each tumor from the same patient has a unique 11p breakpoint on the second allele, suggesting that the “second hit” occurred as an independent genetic event 42–44 . Furthermore, unique CTNNB1 variants in each tumor usually follow WT1 variants 37 .…”

Section: What Is Knownmentioning

confidence: 99%

See 1 more Smart Citation

The pathophysiology of bilateral and multifocal Wilms tumors: What we can learn from the study of predisposition syndromes

Welter

Brzezinski

Treece

et al. 2022

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

Approximately 5% of patients with Wilms tumor present with synchronous bilateral disease. The development of synchronous bilateral Wilms tumor (BWT) is highly suggestive of a genetic or epigenetic predisposition. Patients with known germline predisposition to Wilms tumor (WT1 variants, Beckwith Wiedemann spectrum, TRIM28 variants) have a higher incidence of BWT. This Children's Oncology Group (COG)‐International Society for Pediatric Oncology (SIOP‐) HARMONICA initiative review for pediatric renal tumors details germline genetic and epigenetic predisposition to BWT development, with an emphasis on alterations in 11p15.5 (ICR1 gain of methylation, paternal uniparental disomy, and postzygotic somatic mosaicism), WT1, TRIM28, and REST. Molecular mechanisms that result in BWT are often also present in multifocal Wilms tumor (multiple separate tumors in one or both kidneys). We identify priority areas for international collaborative research to better understand how predisposing genetic or epigenetic factors associate with response to neoadjuvant chemotherapy, oncologic outcomes, and long‐term renal function outcomes.

show abstract