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).

Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.

Purpose: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma that develops sporadically or in Neurofibromatosis type 1 patients. Its development is marked by the inactivation of specific tumor suppressor genes (TSGs): NF1, CDKN2A and SUZ12EED (Polycomb Repressor Complex 2). Each TSG loss can be targeted by particular drug inhibitors and we aimed to systematically combine these inhibitors, guided by TSG inactivation status, to test their precision medicine potential for MPNSTs.

Cancer genetic counseling in Chile: Addressing barriers, confronting challenges, and seizing opportunities in an underserved Latin American Community.

Purpose: Despite the rapid advancements in genomics and the enactment of a new cancer law in Chile, the implementation of cancer genetic counseling continues to face significant challenges because of limited resources and infrastructure.

Methods: We conducted a survey targeting health care providers who offer genetic counseling to patients with cancer and possess training in genetics and counseling. Additionally, we distributed a separate survey to high-risk patients associated with an advocacy group to gather insights on their perceptions of and experiences with cancer genetic counseling.

Using UMAP for Partially Synthetic Healthcare Tabular Data Generation and Validation.

In healthcare, vast amounts of data are increasingly collected through sensors for smart health applications and patient monitoring or diagnosis. However, such medical data often comprise sensitive patient information, posing challenges regarding data privacy, and are resource-intensive to acquire for significant research purposes. In addition, the common case of lack of information due to technical issues, transcript errors, or differences between descriptors considered in different health centers leads to the need for data imputation and partial data generation techniques.