دورية أكاديمية
Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA
| العنوان: | Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA |
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| المؤلفون: | Guler, Gulfem D., Ning, Yuhong, Ku, Chin-Jen, Phillips, Tierney, McCarthy, Erin, Ellison, Christopher K., Bergamaschi, Anna, Collin, Francois, Lloyd, Paul, Scott, Aaron, Antoine, Michael, Wang, Wendy, Chau, Kim, Ashworth, Alan, Quake, Stephen R., Levy, Samuel |
| المصدر: | Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort ( n = 64) in comparison with a non-cancer cohort ( n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function ( GATA4 , GATA6 , PROX1 , ONECUT1 , MEIS2 ), and cancer pathogenesis ( YAP1 , TEAD1 , PROX1 , IGF1 ). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53 . Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-020-18965-w |
| الإتاحة: | https://doi.org/10.1038/s41467-020-18965-wTest https://www.nature.com/articles/s41467-020-18965-w.pdfTest https://www.nature.com/articles/s41467-020-18965-wTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.3B2DFCB8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-18965-w |
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