ABSTRACT
IMPORTANCE: Noninvasive prenatal testing (NIPT) for fetal aneuploidy by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a major prenatal genetic test. Similar to placental DNA, tumor DNA can be detected in the plasma, and analysis of cell-free tumor DNA can be used to characterize and monitor cancers. We show that plasma DNA profiling allows for presymptomatic detection of tumors in pregnant women undergoing routine NIPT. OBSERVATIONS: During NIPT in over 4000 prospective pregnancies by parallel sequencing of maternal plasma cell-free DNA, 3 aberrant genome representation (GR) profiles were observed that could not be attributed to the maternal or fetal genomic constitution. A maternal cancer was suspected, and those 3 patients were referred for whole-body diffusion-weighted magnetic resonance imaging, which uncovered an ovarian carcinoma, a follicular lymphoma, and a Hodgkin lymphoma, each confirmed by subsequent pathologic and genetic investigations. The copy number variations in the subsequent tumor biopsies were concordant with the NIPT plasma GR profiles. CONCLUSIONS AND RELEVANCE: We show that maternal plasma cell-free DNA sequencing for noninvasive prenatal testing also may enable accurate presymptomatic detection of maternal tumors and treatment during pregnancy.
Subject(s)
Biomarkers, Tumor/genetics , DNA, Neoplasm/genetics , Gene Expression Profiling , Genetic Testing/methods , Hodgkin Disease/diagnosis , Lymphoma, Follicular/diagnosis , Ovarian Neoplasms/diagnosis , Pregnancy Complications, Neoplastic/diagnosis , Prenatal Diagnosis/methods , Asymptomatic Diseases , Biomarkers, Tumor/blood , Biopsy , DNA, Neoplasm/blood , Diffusion Magnetic Resonance Imaging , Female , Genetic Predisposition to Disease , Hodgkin Disease/blood , Hodgkin Disease/genetics , Hodgkin Disease/therapy , Humans , In Situ Hybridization, Fluorescence , Lymphoma, Follicular/blood , Lymphoma, Follicular/genetics , Lymphoma, Follicular/therapy , Ovarian Neoplasms/blood , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Phenotype , Predictive Value of Tests , Pregnancy , Pregnancy Complications, Neoplastic/blood , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/therapy , Prognosis , Whole Body ImagingABSTRACT
UNLABELLED: We describe a newborn girl with a life-threatening laryngomalacia and extreme hypotonia. Genetic analysis revealed the very rare genetic condition mosaicism of 48,XXXX and 49,XXXXX (50/50). We here state that the degree of early hypotonia constitutes an important early prognostic feature in this syndrome. The timely insertion of a gastrostomy is warranted in order to prevent aspiration. CONCLUSION: A karyotype is mandatory in female newborns with moderate to severe hypotonia in order to exclude polyploid mosaicism of the X chromosome. An 'overall prognosis' for 48,XXXX and 49,XXXXX girls is difficult to provide towards parents in line with a well-known, substantial variability in outcome for all polysomy X infants.
