Clinicopathologic Features of Breast Tumors in Germline TP53 Variant-Associated Li-Fraumeni Syndrome.

We present one of the largest cohorts of TP53-pathogenic germline variants (PGVs) associated with patients with Li-Fraumeni syndrome (n = 82) with breast tumors (19 to 76 y; median age: 35). Most had missense variants (77%), followed by large gene rearrangements (LGRs; 12%), truncating (6%), and splice-site (5%) variants. Twenty-one unique germline missense variants were found, with hotspots at codons 175, 181, 245, 248, 273, 334, and 337.

Functionally important binding site for a volatile anesthetic in a voltage-gated sodium channel identified by X-ray crystallography.

Volatile general anesthetics are used for inhalational anesthesia in hundreds of millions of surgical procedures annually, yet their mechanisms of action remain unclear. Membrane proteins involved in cell signaling are major targets for anesthetics, and voltage-gated ion channels that mediate neurotransmission, movement, and cognition are sensitive to volatile anesthetics (VAs). In many cases, the effects produced by VAs on mammalian ion channels are reproduced in prokaryotic orthologues, providing an opportunity to investigate VA interactions at high resolution using these structurally simpler prokaryotic proteins.

Breathing new insights into the role of mutant p53 in lung cancer.

The tumour suppressor gene p53 is one of the most frequently mutated genes in lung cancer and these defects are associated with poor prognosis, albeit some debate exists in the lung cancer field. Despite extensive research, the exact mechanisms by which mutant p53 proteins promote the development and sustained expansion of cancer remain unclear. This review will discuss the cellular responses controlled by p53 that contribute to tumour suppression, p53 mutant lung cancer mouse models and characterisation of p53 mutant lung cancer.