PCR-Based Blood Test Diagnoses Rare Childhood Germ Cell Cancer

A team of British researchers has developed a noninvasive, low cost blood test for the diagnosis of rare childhood germ cell cancer.

The five year disease-free and overall survival rates for patients with high-risk malignant germ cell tumors are less than 50%, so improved diagnostic and monitoring techniques are required to improving outcomes for patients. Currently, biopsy is the most commonly used diagnostic method, but this technique is prone to sampling errors and may not be representative of the tumor as a whole. Computerized tomography (CT) scans and magnetic resonance imaging (MRI) also provide useful information but are not diagnostic and do not discriminate between benign and malignant tumors.


Investigators at the University of Cambridge (United Kingdom; www.cam.ac.uk) have now described a noninvasive, low cost blood test for the diagnosis of germ cell tumors.

This test is a qRT–PCR (quantitative real-time PCR [polymerase chain reaction]) profiling analysis of the microRNAs miR–371–373 and miR–302/367 cluster miRNAs, which are overexpressed in all malignant germ cell tumors. Some of these miRNAs show elevated serum levels at diagnosis.

MicroRNAs (miRNAs) are a class of about 20 nucleotides-long RNA fragments that block gene expression by attaching to molecules of messenger RNA (mRNA) in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA. With their capacity to fine-tune protein expression via sequence-specific interactions, miRNAs help regulate cell maintenance and differentiation.

The investigators used their assay to evaluate a total of 45 serum and CSF samples, obtained from 25 pediatric patients. They found that a four-serum miRNA panel (miR–371a–3p, miR–372–3p, miR–373–3p, and miR–367–3p): (i) showed high sensitivity/specificity for diagnosing pediatric extracranial malignant germ cell tumor; (ii) allowed early detection of relapse of a testicular mixed malignant germ cell tumor; and (iii) distinguished intracranial malignant germ cell tumor from intracranial non-germ cell tumors at diagnosis, using CSF and serum samples.


"Although relatively rare, childhood germ cell tumors need to be diagnosed accurately and followed up carefully to give us the best chances of treating them," said senior author Dr. Nicholas Coleman, professor of pathology at the University of Cambridge. "At the moment, we are not good enough at diagnosing these tumors and monitoring their treatment: we need better, safer, and more cost-effective tests."

The study was published in the December 15, 2015, online edition of the British Journal of Cancer.

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