Noninvasive prenatal testing of hereditary colorectal cancer syndromes using cell‐free DNA in maternal plasma

This study aimed to establish a practical protocol for early noninvasive prenatal testing (NIPT) for fetuses at risk of Peutz-Jeghers syndrome or familial adenomatous polyposis, two classical types of hereditary colorectal cancer syndromes, for risk evaluation and whole-life monitoring.Target enrichment was performed using hybridization probes coordinating the serine-threonine kinase 11 gene region and APC gene region, with 1458 highly heterozygous Single Nucleotide Polymorphisms included. Semitarget amplification random sequencing was used for large fragment deletion detection. For relative haplotype dosage (RHDO) analysis, haplotype construction was performed by segmented haplotype estimation and imputation tool software, the circular binary segmentation algorithm was used for recombination event calculation, and Bayes factor was used for the determination of whether the fetus was affected.Haplotypes were successfully constructed in the nine recruited families with different pedigree characteristics, and the results for the RHDO analysis were consistent with the amniocentesis sampling detection results. The cell-free fetal DNA fraction can be detected as low as 2% in maternal plasma.This is the first NIPT assay on hereditary colorectal cancer syndromes based upon RHDO analysis.