TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.

Background: Germline heterozygous pathogenic variants (PVs) in TP53 cause Li-Fraumeni syndrome (LFS), a condition associated with increased risk of multiple tumor types. As the associated cancer risks were refined over time, clinical criteria also evolved to optimize diagnostic yield. The implementation of multi-gene panel germline testing in different clinical settings has led to the identification of TP53 PV carriers outside the classic LFS-associated cancer phenotypes, leading to a broader cancer phenotypic redefinition and to the renaming of the condition as "heritable TP53-related cancer syndrome" (hTP53rc).

Cancer-associated DAXX mutations reveal a critical role for ATRX localization in ALT suppression.

To maintain genome stability, proliferating cells must enact a program of telomere maintenance. While most tumors maintain telomeres through the action of telomerase, a subset of tumors utilize a DNA-templated process termed Alternative Lengthening of Telomeres or ALT. ALT is associated with mutations in the ATRX/DAXX/H3.

Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations.

Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.

Detection of germline CNVs from gene panel data: benchmarking the state of the art.

Germline copy number variants (CNVs) play a significant role in hereditary diseases. However, the accurate detection of CNVs from targeted next-generation sequencing (NGS) gene panel data remains a challenging task. Several tools for calling CNVs within this context have been published to date, but the available benchmarks suffer from limitations, including testing on simulated data, testing on small datasets, and testing a small subset of published tools.

Geographically widespread and novel hemotropic mycoplasmas and bartonellae in Mexican free-tailed bats and sympatric North American bat species.

Unlabelled: Bacterial pathogens remain poorly characterized in bats, especially in North America. We describe novel (and in some cases panmictic) hemoplasmas (10.1% positivity) and bartonellae (25.