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In the works: a better way to detect brain cancers

Chetan Bettegowda, Ludwig Cancer Research Baltimore
Chetan Bettegowda

The paucity of reliable, quantitative biomarkers for the diagnosis and monitoring of cancers of the central nervous system has long been a challenge in discerning nonmalignant lesions from malignant growths in the brain. Dangerous biopsies are the only definitive means of diagnosis for most such cancers. Researchers led by Ludwig Johns Hopkins’ Chetan Bettegowda described in an August paper in Cell Reports Medicine—capped by an award-worthy pun in the headline—an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system by the evaluation of DNA in cerebrospinal fluid (CSF). The method, which involves the PCR amplification of short interspersed nuclear elements (SINEs) using a single primer pair and evaluating the products by next-generation sequencing, assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Applied to 280 CSF samples, the technique correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions using just 1 mL of each sample CSF to perform all assays. The gold standard today, cytology of CSF, has a sensitivity that ranges from 2% to 50%, depending on the type of cancer involved, and requires large amounts (10 mL) of CSF. Real-CSF plasma also proved to be more sensitive than cell–free DNA analysis in samples from the same patients.

Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid
Cell Reports Medicine, 2023 August 15

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