A mononucleotide repeat in PRRT2 is an important, frequent target of mismatch repair deficiency in cancer

The DNA mismatch repair (MMR) system corrects DNA replication mismatches thereby contributing to the maintenance of genomic stability. MMR deficiency has been observed in prostate cancer but its impact on the genomic landscape of these tumours is not known. In order to identify MMR associated mutations in prostate cancer we have performed whole genome sequencing of the MMR deficient PC346C prostate cancer cell line. We detected a total of 1196 mutations in PC346C which was 1.5-fold higher compared to a MMR proficient prostate cancer sample (G089). Of all different mutation classes, frameshifts in mononucleotide repeat (MNR) sequences were significantly enriched in the PC346C sample. As a result, a selection of genes with frameshift mutations in MNR was further assessed regarding its mutational status in a comprehensive panel of prostate, ovarian, endometrial and colorectal cancer cell lines. We identified PRRT2 and DAB2IP to be frequently mutated in MMR deficient cell lines, colorectal and endometrial cancer patient samples. Further characterization of PRRT2 revealed an important role of this gene in cancer biology. Both normal prostate cell lines and a colorectal cancer cell line showed increased proliferation, migration and invasion when expressing the mutated form of PRRT2 (ΔPRRT2). The wild-type PRRT2 (PRRT2wt) had an inhibitory effect in proliferation, consistent with the low expression level of PRRT2 in cancer versus normal prostate samples

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

Cyclam-based molybdenum carbonyl complexes as a novel class of cytotoxic agents

Funding Information: The authors acknowledge Fundação para a Ciência e a Tecnologia, Portugal, for funding within the framework of projects UIDP/00100/2020 (DOI: 10.54499/UIDP/00100/2020), UIDB/ 00100/2020 (DOI: 10.54499/UIDB/00100/2020), LA/P/0056/2020 (DOI: 10.54499/LA/P/0056/2020) and UID/Multi/04349/2020 (DOI: 10.54499/UIDB/04349/2020). Publisher Copyright: © 2025 The Royal Society of Chemistry.Cyclam-based molybdenum carbonyl complexes of formulae [(H2R2Cyclam)Mo(CO)3] (R = H, 4-tBuPhCH24-CF3PhCH2 and 3,5-MePhCH2) were prepared in high yields by the reaction of Mo(CO)6 with the appropriate ligand precursor under reflux in di-n-butyl ether. All complexes were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopy, thermogravimetry as well as single-crystal X-ray diffraction in the case of [(H4Cyclam)Mo(CO)3]. The cytotoxic effect of all compounds was examined on the human breast cancer cells MCF-7 and MDA-MB-231 revealing high antiproliferative activity.publishersversionpublishe