PDF(Pubmed)
Abstract：
Diagnosis of biliopancreatic cancers by the available serum tumor markers, imaging, and histopathological tissue specimen examination remains a challenge. Circulating cell-free DNA derived from matched pairs of secretin-stimulated duodenal fluid (DF) and plasma from 10 patients with biliopancreatic diseases and 8 control subjects was analyzed using AmpliSeq™ HD technology for Ion Torrent Next-Generation Sequencing to evaluate the potential of liquid biopsy with DF in biliopancreatic cancers. The median cfDNA concentration was greater in DF-derived than in plasma-derived samples. A total of 13 variants were detected: 11 vs. 1 were exclusive for DF relative to the plasma source, and 1 was shared between the two body fluids. According to the four-tier systems, 10 clinical tier-I-II (76.9%), 1 tier-III (7.7%), and 2 tier-IV (15.4%) variants were identified. Notably, the 11 tier-I-III variants were exclusively found in DF-derived cfDNA from five patients with biliopancreatic cancers, and were detected in seven genes (KRAS, TP53, BRAF, CDKN2A, RNF43, GNAS, and PIK3CA); 82% of the tier-I-III variants had a low abundance, with a VAF < 6%. The mutational profiling of DF seems to be a reliable and promising tool for identifying cancer-associated alterations in malignant cancers of the biliopancreatic tract.
摘要：
通过可用的血清肿瘤标志物诊断胆胰癌，成像,和组织病理学组织标本检查仍然是一个挑战。使用AmpliSeq™HD技术进行离子激流下一代测序，分析了来自10名胆胰疾病患者和8名对照受试者的配对的促胰液（DF）和血浆对的循环无细胞DNA，以评估具有DF的液体活检在胆胰癌中的潜力。DF来源的cfDNA浓度中位数高于血浆来源的样品。总共检测到13种变体：11vs.1只用于DF，相对于等离子体源，1在两种体液之间共享。根据四级系统，10临床一级-二级（76.9%），1个三级（7.7%），并鉴定了2个IV级（15.4%）变异。值得注意的是,这11个I-III级变异仅在来自5例胆胰癌患者的DF来源的cfDNA中发现，并在七个基因中检测到(KRAS，TP53,BRAF,CDKN2A,RNF43,GNAS,和PIK3CA）；82%的I-III级变体具有低丰度，VAF<6%。DF的突变分析似乎是鉴定胆胰道恶性肿瘤中与癌症相关的改变的可靠且有前途的工具。
