RESUMO
PURPOSE: We set out to facilitate the molecular diagnosis of patients with PIK3CA-related overgrowth spectrum (PROS), a heterogeneous somatic disorder characterized by variable presentations of segmental overgrowth, vascular malformations, skin lesions, and nephroblastomatosis, rare precursor lesions to Wilms tumor. Molecular diagnosis of PROS is challenging due to its mosaic nature, often requiring invasive biopsies. METHODS: Digital droplet polymerase chain reaction (ddPCR) was used to analyze tissues including urine, saliva, buccal cells, and blood, from eight patients with PROS. Further analyses were performed on plasma and urine cell-free DNA (cfDNA). RESULTS: PIK3CA variants were detected in plasma cfDNA at levels up to 0.5% in 50% of tested samples. In addition, high levels of PIK3CA variants in urine cfDNA correlated with a history of nephroblastomatosis compared with patients without renal involvement (P < 0.05). CONCLUSION: Digital droplet PCR is a sensitive molecular tool that enables low-level variant detection of PIK3CA in various tissue types, providing an alternative diagnostic method. Furthermore, urine cfDNA is a candidate biomarker for nephroblastomatosis in PROS, which may be useful to refine screening guidelines for tumor risk in these patients.
Assuntos
Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/urina , Macrossomia Fetal/urina , Tumor de Wilms/urina , Adulto , Biomarcadores/urina , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Macrossomia Fetal/genética , Estudos de Associação Genética , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Humanos , Masculino , Mutação , Doenças Raras/genética , Doenças Raras/urina , Tumor de Wilms/genéticaRESUMO
OBJECTIVE: Our objective was to determine if early pregnancy urinary metabolomic profiles could predict fetal adiposity and macrosomia. METHODS: This is a prospective study of 50 healthy women in their second pregnancy. Fasting urine samples taken during early pregnancy were analyzed using NMR spectroscopy. Maternal glucose and insulin were measured in early pregnancy and at 28 weeks and the HOMA index for insulin resistance calculated. At 34 weeks ultrasound assessed fetal anthropometry including fetal anterior abdominal wall width (AAW). At delivery birth weight was recorded. Probabilistic principal component with covariates analysis (PPCCA), a novel extension of principal component analysis, which facilitates joint modeling of metabolomic data and additional covariate information, was employed to analyze the data. RESULTS: This analysis revealed that maternal HOMA and AAW significantly covaried with the (1)H NMR derived metabolomic profile of the urine. As such, in this cohort of healthy, non-diabetic women, early pregnancy urinary metabolomic profile differed significantly according to both maternal insulin resistance and fetal fat deposition in utero. CONCLUSION: These findings hold potential for early pregnancy identification of those at risk of fetal macrosomia.
