METHODS: These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM).
OBJECTIVE: For adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation?
CONCLUSIONS: Level III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient\'s clinical course is as expected.
OBJECTIVE: For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal?
CONCLUSIONS: Level III: Repeat MGMT promoter methylation is not recommended.
OBJECTIVE: For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated?
CONCLUSIONS: Level III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered.
OBJECTIVE: For adult patients with progressive glioblastoma does large panel or whole genome sequencing provide management or prognostic information beyond that derived from histologic analysis?
CONCLUSIONS: Level III: Primary or repeat large panel or whole genome sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials.
OBJECTIVE: For adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis?
CONCLUSIONS: Level III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing.
OBJECTIVE: For adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis?
CONCLUSIONS: Level III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline.

DNA methyltransferases (DNMTs) play an essential role in DNA methylation and transcriptional regulation in the genome. DNMTs, along with other poorly studied elements, modulate the dynamic DNA methylation patterns of embryonic and adult cells. We summarize the current knowledge on the molecular mechanism of DNMTs\' functional targeting to maintain genome-wide DNA methylation patterns. We focus on DNMTs\' intrinsic characteristics, transcriptional regulation, and post-transcriptional modifications. Furthermore, we focus special attention on the DNMTs\' specificity for target sites, including key cis-regulatory factors such as CpG content, common motifs, transcription factors (TF) binding sites, lncRNAs, and histone marks to regulate DNA methylation. We also review how complexes of DNMTs/TFs or DNMTs/lncRNAs are involved in DNA methylation in specific genome regions. Understanding these processes is essential because the spatiotemporal regulation of DNA methylation modulates gene expression in health and disease.

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We describe a new primer design strategy for PCR amplification of unknown targets that are related to multiply-aligned protein sequences. Each primer consists of a short 3\' degenerate core region and a longer 5\' consensus clamp region. Only 3-4 highly conserved amino acid residues are necessary for design of the core, which is stabilized by the clamp during annealing to template molecules. During later rounds of amplification, the non-degenerate clamp permits stable annealing to product molecules. We demonstrate the practical utility of this hybrid primer method by detection of diverse reverse transcriptase-like genes in a human genome, and by detection of C5DNA methyltransferase homologs in various plant DNAs. In each case, amplified products were sufficiently pure to be cloned without gel fractionation. This COnsensus-DEgenerate Hybrid Oligonucleotide Primer (CODEHOP) strategy has been implemented as a computer program that is accessible over the World Wide Web (http://blocks.fhcrc.org/codehop.html) and is directly linked from the BlockMaker multiple sequence alignment site for hybrid primer prediction beginning with a set of related protein sequences.