Abstract
Telomerase reverse transcriptase promoter (TERTp) hotspot mutations are the most frequent mutations in primary glioblastomas (GBM). Previous studies have shown that the combination of TERTp and isocitrate dehydrogenase (IDH) status may serve as a useful diagnostic marker for oligodendroglioma and glioblastoma. In oligodendrogliomas, TERTp and IDH mutations, along with the 1p/19q codeletion, usually coexist and are likely to be founder mutations. However, in contrast to oligodendroglioma, the role of the TERTp status in GBM remains obscure. Here, we used Sanger sequencing, pyrosequencing, and digital PCR (dPCR) to examine the TERTp status in 15 pairs of frozen tissue samples from primary and recurrent IDH wild-type GBM, all of which were operated in a single institute. We showed that the TERTp status was stable between primary and recurrent GBM but this consistency was only detected by dPCR. The results suggest that dPCR is a powerful, highly sensitive tool to detect TERTp mutations, especially in a mixed cell population (e.g., a recurrent GBM tissue) where earlier treatment may have grossly altered the tumor microenvironment.
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Acknowledgments
K.I. was supported by the Japan Cancer Research Project and Practical Research for Innovative Cancer Control programs from the Japan Agency for Medical Research and Development (AMED).
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All procedures involving patients were performed in accordance with the ethical standards of the National Cancer Center and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained to use tumor material according to the procedures outlined by the National Cancer Center.
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Miki, S., Satomi, K., Ohno, M. et al. Highly sensitive detection of TERT promoter mutations in recurrent glioblastomas using digital PCR. Brain Tumor Pathol 37, 154–158 (2020). https://doi.org/10.1007/s10014-020-00375-x
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DOI: https://doi.org/10.1007/s10014-020-00375-x