RESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/genética , ADN de Neoplasias/genética , Perfilación de la Expresión Génica , Pruebas Genéticas/métodos , Enfermedad de Hodgkin/diagnóstico , Linfoma Folicular/diagnóstico , Neoplasias Ováricas/diagnóstico , Complicaciones Neoplásicas del Embarazo/diagnóstico , Diagnóstico Prenatal/métodos , Enfermedades Asintomáticas , Biomarcadores de Tumor/sangre , Biopsia , ADN de Neoplasias/sangre , Imagen de Difusión por Resonancia Magnética , Femenino , Predisposición Genética a la Enfermedad , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/terapia , Humanos , Hibridación Fluorescente in Situ , Linfoma Folicular/sangre , Linfoma Folicular/genética , Linfoma Folicular/terapia , Neoplasias Ováricas/sangre , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Fenotipo , Valor Predictivo de las Pruebas , Embarazo , Complicaciones Neoplásicas del Embarazo/sangre , Complicaciones Neoplásicas del Embarazo/genética , Complicaciones Neoplásicas del Embarazo/terapia , Pronóstico , Imagen de Cuerpo EnteroRESUMEN
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.