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Replicative immortality is a hallmark of cancer cells governed by telomere maintenance. Approximately 90% of human cancers maintain their telomeres by activating telomerase, driven by the transcriptional upregulation of telomerase reverse transcriptase (TERT). Although TERT promoter mutations (TPMs) are a major cancer-associated genetic mechanism of TERT upregulation, many cancers exhibit TERT upregulation without TPMs. In this study, we describe the TERT hypermethylated oncological region (THOR), a 433-bp genomic region encompassing 52 CpG sites located immediately upstream of the TERT core promoter, as a cancer-associated epigenetic mechanism of TERT upregulation. Unmethylated THOR repressed TERT promoter activity regardless of TPM status, and hypermethylation of THOR counteracted this repressive function. THOR methylation analysis in 1,352 human tumors revealed frequent (>45%) cancer-associated DNA hypermethylation in 9 of 11 (82%) tumor types screened. Additionally, THOR hypermethylation, either independently or along with TPMs, accounted for how approximately 90% of human cancers can aberrantly activate telomerase. Thus, we propose that THOR hypermethylation is a prevalent telomerase-activating mechanism in cancer that can act independently of or in conjunction with TPMs, further supporting the utility of THOR hypermethylation as a prognostic biomarker.

We explore the biomarker potential of the TERT hypermethylated oncologic region (THOR) in pancreatic cancer. We assessed the methylation status of THOR using the cancer genome atlas data on the cohort of pancreatic cancer (n = 193 patients). THOR was significantly hypermethylated in pancreatic tumor tissue when compared with the normal tissue used as control (p < 0.0001). Also, THOR hypermethylation could distinguish early stage I disease from normal tissue and was associated with worse prognosis. We found that THOR is hypermethylated in pancreatic tumor tissue when compared with normal tissue and that THOR methylation correlates with TERT expression in tumor samples. Our preliminary findings support the diagnostic and prognostic values of THOR in pancreatic cancer.

Since THOR was shown to associate with TERT expression (3), our group investigated TERT expression in pancreatic cancer and found a positive correlation with THOR methylation levels. The authors (12) suggested that ofCS could play a key role in tumor-cell motility through integrin signaling pathways, and therefore supports the metastatic potential of cancer cells (13). Testing a wide range of cells and tissues, the authors found that the recombinant VAR2CSA protein binds >95% of cancer cell lines and tissues of epithelial, mesenchymal and hematopoietic origin, with very limited binding to noncancerous cells or normal tissue (besides placental tissue), which it could improve its role as tool to broadly and efficiently capture rare cancer cells in complex blood samples (10,12). [...]more robust and well-designed clinical trials are important to assess the role of all these aforementioned biomarkers in the pancreatic cancer framework.

The Breakthrough Listen Initiative is conducting a program using multiple telescopes around the world to search for \"technosignatures\": artificial transmitters of extraterrestrial origin from beyond our solar system. The VERITAS Collaboration joined this program in 2018, and provides the capability to search for one particular technosignature: optical pulses of a few nanoseconds duration detectable over interstellar distances. We report here on the analysis and results of dedicated VERITAS observations of Breakthrough Listen targets conducted in 2019 and 2020 and of archival VERITAS data collected since 2012. Thirty hours of dedicated observations of 136 targets and 249 archival observations of 140 targets were analyzed and did not reveal any signals consistent with a technosignature. The results are used to place limits on the fraction of stars hosting transmitting civilizations. We also discuss the minimum-pulse sensitivity of our observations and present VERITAS observations of CALIOP: a space-based pulsed laser onboard the CALIPSO satellite. The detection of these pulses with VERITAS, using the analysis techniques developed for our technosignature search, allows a test of our analysis efficiency and serves as an important proof-of-principle.