CMV and glioma–are we there yet?

摘要: Findings describing the potential role of human cytomegalovirus (HCMV) infection in glioblastoma (GBM) have been controversial since their initial description 2002.1 We hope to provide some perspective on evolution and, hopefully, offer suggestions about how move forward a constructive fashion. With regard HCMV glioma, difficulties arriving at definitive conclusions are due part technical intricacies detecting viral epitopes by immunohistochemistry (IHC) as well lack success ancillary corroborating methodologies demonstrate virus brain tumors. These factors generated healthy degree skepticism and caution, which, our opinion, is warranted until findings can be reasonably proven accepted basis totality evidence. In this regard, we borrow phrase often used legal system, that reasonable doubt. As applied case, it probably wisest retain doubt glioma its relevance widely reproduced. Continuing analogy, burden proof best placed those making claim, caution absence clear convincing data. A paper issue Neuro-Oncology Baumgarten et al.2 reports an inability detect GBM, casting further glioma. Robust scientific should based evidence from complementary sources mutual support for consensus conclusion. Accordingly, absent detection methods (mRNA, DNA sequencing, etc) invites pathogenic may play GBM. Reliance one method, like IHC, under specific set iron-clad conditions raises red flags terms drawing conclusions. Even when read convincingly positive, IHC misleading, illustrated well-recognized cross-reactivity antikeratin antibodies GBM.3 Directly point recent failed identify using high-coverage unbiased/whole genome sequencing 34 samples GBM.4 While does not rule out low-level important note HHV4 (Epstein-Barr) other sequences were identified, suggesting abundance would exceed 1 per 240 000 tumor cells even if present. Similarly, additional studies RNA yielded GBM.5–7 The absolute extremely difficult prove definitively way, al. Instead, report details carefully performed study signal setting which known positive controls order. title indicates, was detected 123 standard techniques settings. One always argue limitations assay preclude detection, antigen only had done differently or processed appropriately, etc. most judicious approach reached evidence, ideally diverse sources. setting, believe date warrant conclusion present GBM. In fairness proponents hypothesis, HCMV. However, saying goes, construed absence. fair might undetectable given samples, approach. light, represents contribution literature whole. Moving forward, must remain open possibility improved future allow widespread reliable across laboratories, robustly reproduced independently confirmed range assays with appropriate analytical clinical validity, conclude “the jury still out” respect glioma.