GC-10: A PROPOSED PATHWAY TOWARDS NON-INVASIVE microRNA-BASED DIAGNOSIS AND RISK STRATIFICATION OF CNS MALIGNANT GERM CELL TUMOURS

INTRODUCTION: The protein biomarkers alpha-fetoprotein and human chorionic gonadotropin currently used to diagnose malignant germ cell tumours (MGCTs) have limited sensitivity/specificity. ‘Marker-negative’ CNS-MGCT cases require biopsy, which carries substantial morbidity/mortality risks. Improved, minimally-invasive tests are therefore required to a) segregate CNS-MGCTs from other CNS lesions and b) discriminate between the marker-negative CNS-MGCT subtypes embryonal carcinoma and germinoma. We are currently developing microRNA-based tests to achieve the above aims, having previously identified a panel of four microRNAs (miR-371a-3p/miR-372-3p/miR-373-3p/miR-367-3p; miR-371 ∼ 3/367) that are elevated in extracranial-MGCT patient serum at diagnosis, which segregates extracranial-MGCTs from extracranial benign-GCTs/other malignancies. METHODS: Using qRT-PCR, we quantified miR-371 ∼ 3/367 levels at diagnosis in CSF and available matched-serum from patients with (suprasellar/pineal) CNS-MGCTs (n = 5) versus other CNS lesions (n = 3; low-grade-glioma, LCH, intracranial-relapsed neuroblastoma), plus serum from 7 other CNS lesions [low-grade-glioma (n = 6), medulloblastoma (n = 1)], and 8 non-malignant-controls. RESULTS: CSF miR-371 ∼ 3/367 levels were elevated in all five patients with CNS-MGCTs, compared with other CNS lesions. For the three CNS-MGCT patients where matching serum was available, serum levels of miR-371 ∼ 3/367 were also elevated when compared with serum levels in other CNS lesions and non-malignant-controls. CONCLUSIONS: Serum and CSF levels of miR-371 ∼ 3/367 reliably detect CNS-MGCTs at diagnosis. At present we are identifying serum/CSF microRNAs that differentiate between marker-negative embryonal carcinoma and germinoma subtypes of CNS-MGCTs. Our overall approach will ultimately assist both non-invasive CNS-MGCT diagnosis and risk-stratification, and thus inform subsequent treatment-planning.