TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors

Background: Giant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than "classic" IDHwt GBM. Methods: We studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data. Results: p53 was altered by gene mutation or protein overexpression in all cases, while driver IDH1, IDH2, BRAF, or H3F3A mutations were infrequent or absent. Compared to IDHwt GBMs, gcGBMs had a significant higher frequency of TP53, ATRX, RB1, and NF1 mutations, while lower frequency of EGFR amplification, CDKN2A deletion, and TERT promoter mutation. Almost all tumors had low TML values. The high TML observed in only 2 tumors was consistent with POLE and MSH2 mutations. In the histopathological review of TCGA IDHwt, TP53-mutant tumors identified giant cells in 37% of the cases. Considering our series and that of the TCGA, patients with TP53-mutant gcGBMs had better overall survival than those with TP53wt GBMs (log-rank test, P < .002). Conclusions: gcGBMs have molecular features that contrast to "classic" IDHwt GBMs: unusually frequent ATRX mutations and few EGFR amplifications and CDKN2A deletions, especially in tumors with a high number of giant cells. TML is frequently low, although exceptional high TML suggests a potential for immune checkpoint therapy in some cases, which may be relevant for personalized medicine

A multi technical study of silver denars from medieval Poland for improved understanding of their archaeological context and provenance

This paper discusses a methodology that involves the use of x amp; 8208;ray fluorescence XRF , high energy particle induced x amp; 8208;ray emission HE amp; 8208;PIXE and particle induced amp; 947; amp; 8208;ray emission HE amp; 8208;PIGE spectroscopies for the study of historic denars with the aim of describing the advantages and limitations of each technique as well as arriving at an archaeometric interpretation of the compositions. Thirty nine medieval Polish denars minted by Kings Boles amp; 322;aw the Brave and Mieszko II Lambert were analysed for their elemental composition. While XRF is limited to the analysis of the material close to the object s surface, high energy ion beam analysis was used to obtain information from Cu at a relatively larger depth. The major elements detected were Ag and Cu, while the minor elements were Pb, Au, Bi, and Zn. An evaluation of the results obtained with the different techniques shows that the content of Cu near the surface is different from the bulk composition of the coins. The obtained elemental composition was used to proliferate the understanding of chronological changes in the production of early medieval Polish denar

Lymphocryptovirus phylogeny and the origins of Epstein-Barr virus

Specimens from wild and captive primates were collected and novel members of the genus Lymphocryptovirus (subfamily Gammaherpesvirinae) were searched for utilizing PCR for the DNA polymerase gene. Twenty-one novel viruses were detected. Together with previous findings, more than 50 distinct lymphocryptoviruses (LCVs) are now known, with hosts from six primate families (Hominidae, Hylobatidae, Cercopithecidae, Atelidae, Cebidae and Pitheciidae). Further work extended genomic sequences for 25 LCVs to 3.4-7.4 kbp. Phylogenetic trees were constructed, based on alignments of protein sequences inferred from the LCV genomic data. The LCVs fell into three major clades: Clade A, comprising New World viruses; Clade B, containing both Old World monkey viruses and hominoid viruses including Epstein-Barr virus (EBV); and Clade C, containing other hominoid viruses. By comparison with the primate tree, it was proposed that major elements of the LCV tree represented synchronous evolution with host lineages, with the earliest node in both trees being the separation of Old and New World lines, but that some virus lineages originated by interspecies transfer. From comparisons of branch lengths, it was inferred that evolutionary substitution in Clade B has proceeded more slowly than elsewhere in the LCV tree. It was estimated that in Clade B a subclade containing EBV, a gorilla virus and two chimpanzee viruses derived from an Old World monkey LCV line approximately 12 million years ago, and another subclade containing an orang-utan virus and a gibbon virus derived from a macaque LCV line approximately 1.2 million years ago