Clinical Characterization of a National Cohort of Patients With Germline Variants Including Late-Onset Phenotypes.

Introduction: disorder is a recently introduced term for phenotypes associated with germline Wilms Tumor 1 () variants, including glomerulopathy, urogenital anomalies, and Wilms tumor. Previous studies showed a bias toward missense variants in the DNA-binding/Zinc-finger domain of (exon 8 and 9) and patients with early-onset glomerulopathy. Thorough genotype-phenotype correlations including follow-up data on late-onset glomerulopathy risk are lacking.

Liver X receptor unlinks intestinal regeneration and tumorigenesis.

Uncontrolled regeneration leads to neoplastic transformation. The intestinal epithelium requires precise regulation during continuous homeostatic and damage-induced tissue renewal to prevent neoplastic transformation, suggesting that pathways unlinking tumour growth from regenerative processes must exist. Here, by mining RNA-sequencing datasets from two intestinal damage models and using pharmacological, transcriptomics and genetic tools, we identified liver X receptor (LXR) pathway activation as a tissue adaptation to damage that reciprocally regulates intestinal regeneration and tumorigenesis.

A tutorial on aggregating evidence from conceptual replication studies using the product Bayes factor.

The product Bayes factor (PBF) synthesizes evidence for an informative hypothesis across heterogeneous replication studies. It can be used when fixed- or random effects meta-analysis fall short. For example, when effect sizes are incomparable and cannot be pooled, or when studies diverge significantly in the populations, study designs, and measures used.

Mutational mechanisms in multiply relapsed pediatric acute lymphoblastic leukemia.

Pediatric acute lymphoblastic leukemia (ALL) is marked by low mutational load at initial diagnosis, which increases at relapse. To determine which processes are active in (relapsed) ALL and how they behave during disease progression before and after therapy, we performed whole genome sequencing on 97 tumor samples of 29 multiply relapsed ALL patients. Mutational load increased upon relapse in 28 patients and upon every subsequent relapse in 22 patients.