Nat Commun: Detection of early pancreatic cancer with free DNA.

Pancreatic cancer is often detected as advanced and the symptoms are not obvious, when only 10-20% of patients are eligible for surgical removal.
pancreatic catheter adenocarcinoma (PDAC) accounts for more than 90% of all pancreatic cancer cases, followed by neuroendocrine tumors.
pancreatic catheter adenocarcinoma (PDAC) accounts for more than 90% of all pancreatic cancer cases, followed by neuroendocrine tumors.
smoking increases the risk of pancreatic cancer by 2-3 times, and contributes to about 15-30% of cases in which smokers are diagnosed 8-15 years younger than nonsmosts.
family history can also contribute to about 10% of cases.
strain mutations in genes such as BRCA2, BRCA1, CDKN2A, ATM, STK11, PRSS1, MLH1, and PALB2 are associated with variable penetration of pancreatic cancer.
Transformational studies using genomic and proteomic techniques have provided molecular insights into the pathogenesis and biology of pancreatic cancer, but have not yet produced strong diagnostic biomarkers to influence early diagnosis of the disease, as reflected in a low overall five-year survival rate of 10%.
Recently, researchers in Nature Communications described changes in circulating cell free DNA through 5-hydroxymed methyl cytosine (5hmC), non-invasive detection of pancreatic catheter cancer (PDAC) in PDAC queues (n s 64) and non-cancer queues (n s 243).
differential hydroxy methylation is found in thousands of genes, most notably 1 genes associated with pancreatic development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and genes associated with cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1).
results showed that after KRAS activation and TP53 inactivation, the differences in the cfDNA hydroxymide group in the PDAC queue were found in genes that are usually regulated in PDAC tumors.
AAUC (discovery dataset, n s 79) and 0.92-0.94 (two independent test sets, n s 228) using a normalized regression model built with 5hmC density in the gene.
addition, tissue-derived 5hmC characteristics can be used to classify PDAC cfDNA (AUC s 0.88).
results suggest that PDAC can be classified based on changes in 5hmC even during early disease.
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