Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA.

Autor: Guler GD; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA., Ning Y; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA., Ku CJ; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA., Phillips T; Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA., McCarthy E; Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA., Ellison CK; Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA., Bergamaschi A; Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA., Collin F; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA., Lloyd P; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA., Scott A; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA., Antoine M; Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA., Wang W; Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA., Chau K; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA., Ashworth A; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA., Quake SR; Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA, 94304, USA.; Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA., Levy S; Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA. slevy@bluestargenomics.com.; Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA. slevy@bluestargenomics.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Oct 19; Vol. 11 (1), pp. 5270. Date of Electronic Publication: 2020 Oct 19.
DOI: 10.1038/s41467-020-18965-w
Abstrakt: 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.
Databáze: MEDLINE
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