| Autor: |
Lamis Yehia, Ying Ni, Tammy Sadler, Thomas W. Frazier, Charis Eng |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
npj Genomic Medicine, Vol 7, Iss 1, Pp 1-9 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2056-7944 |
| DOI: |
10.1038/s41525-022-00289-x |
| Popis: |
Abstract PTEN hamartoma tumor syndrome (PHTS), caused by germline PTEN mutations, has been associated with organ-specific cancers and autism spectrum disorder (ASD) and/or developmental delay (DD). Predicting precise clinical phenotypes in any one PHTS individual remains impossible. We conducted an untargeted metabolomics study on an age- and sex-matched series of PHTS individuals with ASD/DD, cancer, or both phenotypes. Using agnostic metabolomic-analyses from patient-derived lymphoblastoid cells and their spent media, we found 52 differentially abundant individual metabolites, 69 cell/media metabolite ratios, and 327 pair-wise metabotype (shared metabolic phenotype) ratios clearly distinguishing PHTS individuals based on phenotype. Network analysis based on significant metabolites pointed to hubs converging on PTEN-related insulin, MAPK, AMPK, and mTOR signaling cascades. Internal cross-validation of significant metabolites showed optimal overall accuracy in distinguishing PHTS individuals with ASD/DD versus those with cancer. Such metabolomic markers may enable more accurate risk predictions and prevention in individual PHTS patients at highest risk. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink