Patients with telomere biology disorders show context specific somatic mosaic states with high frequency of U2AF1 variants.

Somatic mosaic states in telomere biology disorders are characterized by somatic variants in the spliceosome and DNA damage response and repair pathways. A likely maladaptive response to short telomeres that may lead to increased hematological cancer.

Germline Abnormalities in DNA Methylation and Histone Modification and Associated Cancer Risk.

PURPOSE OF REVIEW: Somatic mutations in DNA methyltransferases and other DNA methylation associated genes have been found in a wide variety of cancers. Germline mutations in these genes have been associated with several rare hereditary disorders. Among the described germline/congenital disorders, neurological dysfunction and/or growth abnormalities appear to be a common phenotype. Here, we outline known germline abnormalities and examine the cancer risks associated with these mutations. RECENT FINDINGS: The increased use and availability of sequencing techniques in the clinical setting has expanded the identification of germline abnormalities involving DNA methylation machinery. This has provided additional cases to study these rare hereditary disorders and their predisposition to cancer. Studying these syndromes may offer an opportunity to better understand the contribution of these genes in cancer development.

A Computational Re-examination of the Criegee Intermediate-Sulfur Dioxide Reaction.

The atmospheric oxidation of sulfur dioxide by the parent and dimethyl Criegee intermediates (CIs) may be an important source of sulfuric acid aerosol, which has a large impact on radiative forcing and therefore upon climate. A number of computational studies have considered how the CH2OOS(O)O heteroozonide (HOZ) adduct formed in the CI + SO2 reaction converts SO2 to SO3. In this work we use the CBS-QB3 quantum chemical method along with equation-of-motion spin-flip CCSD(dT) and MCG3 theories to reveal new details regarding the formation and decomposition of the endo and exo conformers of the HOZ. Although ∼75% of the parent CI + SO2 reaction is initiated by formation of the exo HOZ, hyperconjugation preferentially stabilizes many of the endo intermediates and transition structures by 1-5 kcal mol(-1). Our quantum chemical calculations, in conjunction with statistical rate theory models, predict a rate coefficient for the parent CI + SO2 reaction of 3.68 × 10(-11) cm(3) molecule(-1) s(-1), in good agreement with recent experimental measurements. RRKM/master equation simulations based on our quantum chemical data predict a prompt carbonyl + SO3 yield of >95% for the reaction of both the parent and dimethyl CI with SO2. The existence of concerted cycloreversion transition structures 10-15 kcal mol(-1) higher in energy than the HOZ accounts for most of the predicted SO3 formation.