Non-invasive prenatal testing (NIPT): Combination of copy number variant and gene analyses using an "in-house" target enrichment next generation sequencing-Solution for non-centralized NIPT laboratory?

OBJECTIVE: Recent studies have integrated copy number variant (CNV) and gene analysis using target enrichment. Here, we transferred this concept to our routine genetics laboratory, which is not linked to centralized non-invasive prenatal testing (NIPT) facilities. METHOD: From a cohort of 100 pregnant women, 22 were selected for the analysis of maternal genomic DNA (gDNA) along with fetal cell-free DNA. Using targeted enrichment, 135 genes were analyzed, combined with aberrations of chromosomes 21, 18, 13, X, and Y. The data were subjected to specificity and sensitivity analyses, and correlated with the results from invasive testing methods. RESULTS: The sensitivity/specificity was determined for the CNV analysis of chromosomes: 21 (80%/75%), 18 (-/82%), 13 (100%/67%), and Y (100%/100%). The gene detection was valid for maternal gDNA. However, for cell-free fetal DNA, it was not possible to determine the boundary between an artifact and a real sequence variant. CONCLUSION: The target enrichment method combining CNV and gene detection seems feasible in a regular laboratory. However, this method can only be responsibly optimized with a sufficient number of controls and further validation on a strong bioinformatic background. The present results showed that NIPT should be performed in specialized centers, and that its introduction to isolated laboratories may not provide valid data.

Identification of five new families strengthens the link between childhood choroid plexus carcinoma and germline TP53 mutations.

We present five families of paediatric patients suffering from choroid plexus carcinoma in which we found germline TP53 mutations. Only one of the families conformed to the criteria of Li-Fraumeni syndrome and only three (including the Li-Fraumeni syndrome family) met the Chompret criteria for germline TP53 mutation testing. In the remaining two families no family history of cancer was identified and/or the parents of the patient were shown not to carry the mutation. Our results give further support to the notion that the occurrence of this rare paediatric tumour, especially in combination with a positive family history of cancer, but possibly also without any family history, may be an indicator of a germline TP53 mutation. The identification of this genetic defect has important consequences for cancer prevention and treatment in affected families.