Maternal cancer research (Phase II)

Several studies have associated multiple chromosomal aneuploidies (MCAs) detected in NIPTs with maternal malignancy. After the first case described by Osborn et al in 2013, several subsequent studies have described maternal cancer within failed NIPT tests due to MCAs. In 2015, Bianchi discovered 10 maternal cancer cases from 125,426 pregnancies based on aneuploidies involving chromosomes 13, 18, 21, X, or Y in NIPT tests; eight of the 10 cases showed nonspecific copy-number gains and losses across multiple chromosomes. In 2017, Dharajiya detected 18 maternal malignancies in 43 failed NIPT cases with altered genomic profiles. These studies suggest that MCAs in NIPTs may indicate occult maternal malignancy, yet the sensitivity and specificity of MCAs alone are far too low to be useful in clinical practice.To the best of our knowledge, this is the largest study about the association between MCAs and maternal malignancy. We developed a method for combining MCA findings with whole-genome profiling of copy number variations, and the method in combination with serum tumor markers showed good diagnostic performance in the detection of pre-symptomatic maternal cancer.This study provides evidence that MCAs results can be finely translated into clinical use for identifying maternal malignancy. Maternal malignancy can be detected with significantly higher sensitivity and PPV using the methods than using MCAs alone. The additional use of serum tumour markers allows determination of the primary tumour origin, which can help guide further clinical evaluation of suspected cancer cases.