Genomic analysis of pancreatic juice DNA assesses malignant risk of intraductal papillary mucinous neoplasm of pancreas
Genomic analysis of pancreatic juice DNA assesses malignant risk of intraductal papillary mucinous neoplasm of pancreas
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DOI：
10.1002/cam4.2340
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发表时间：
2019-08-01
期刊：
影响因子：
4
通讯作者：
Fujita, Masashi
中科院分区：
文献类型：
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作者：
Mateos, Raul N.;Nakagawa, Hidewaki;Fujita, Masashi
胰腺导管内乳头状黏液性肿瘤（IPMN）有很高的发展为浸润性癌或与恶性病变并存的风险。因此，通过微创方法评估其恶性风险是非常重要的。胰液游离DNA（PJD）是一种理想的材料，但用于预测PJD恶性风险的遗传生物标志物尚未建立。我们在此对39例有或无恶性病变的IPMN患者的PJD进行了深度外显子组测序分析。将PJD中检测到的体细胞改变和拷贝数改变（CNAs）与IPMN的组织学分级进行比较，以评估其作为恶性肿瘤标志物的潜力。KRAS、GNAS、TP 53和RNF 43的体细胞突变在IPMN的PJD中常见，但与组织学分级无关，而与组织学分级呈正相关（r = 0.427，P = 0.015）。我们还观察到PJD中17 p13（TP 53）的频繁拷贝数缺失和7 q21和8 q24（MYC）的扩增。7 q21和8 q24的扩增与组织学分级呈正相关，在浸润性癌中最常见（分别为P = 0.002和7/11; P = 0.011和6/11）。我们的结论是，PJD中检测到的突变负荷和CNA可能具有评估IPMN恶性进展风险的潜力。
Intraductal papillary mucinous neoplasm (IPMN) of pancreas has a high risk to develop into invasive cancer or co-occur with malignant lesion. Therefore, it is important to assess its malignant risk by less-invasive approach. Pancreatic juice cell-free DNA (PJD) would be an ideal material in this purpose, but genetic biomarkers for predicting malignant risk from PJD are not yet established. We here performed deep exome sequencing analysis of PJD from 39 IPMN patients with or without malignant lesion. Somatic alterations and copy number alterations (CNAs) detected in PJD were compared with the histologic grade of IPMN to evaluate their potential as a malignancy marker. Somatic mutations of KRAS, GNAS, TP53, and RNF43 were commonly detected in PJD of IPMNs, but no association with the histologic grades of IPMN was found. Instead, mutation burden was positively correlated with the histologic grade (r = 0.427, P = 0.015). We also observed frequent copy number deletions in 17p13 (TP53) and amplifications in 7q21 and 8q24 (MYC) in PJDs. The amplifications in 7q21 and 8q24 were positively correlated with the histologic grade and most prevalent in the cases of invasive carcinoma (P = 0.002 and 7/11; P = 0.011 and 6/11, respectively). We concluded that mutation burden and CNAs detected in PJD may have potential to assess the malignant progression risk of IPMNs.