Identification of microRNAs From the miR-371~373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors.

Current serum biomarkers for diagnosis and monitoring of malignant germ cell tumors (GCTs) show limited sensitivity and specificity. We previously observed that microRNAs of the miR-371∼373 and miR-302 clusters are overexpressed in all malignant GCTs, regardless of patient age, histologic subtype, or anatomic site, but are not reported to be coordinately up-regulated in other tumor types or disease states. Herein we show that levels of all 8 main members of the miR-371∼373 and miR-302 clusters were elevated in the serum of a 4-year-old boy at the time of diagnosis of yolk sac tumor. Levels returned to normal during an uneventful clinical follow-up, with kinetics similar to those of the conventional marker α-fetoprotein. We describe in detail the multiplex polymerase chain reaction protocol used to quantify serum microRNA levels, which is highly robust and reproducible. Our study indicates that miR-371∼373 and miR-302 cluster microRNAs are promising candidate biomarkers for improving disease monitoring (and potentially diagnosis) in malignant GCTs.