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Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct.
Gastroenterology ( IF 29.4 ) Pub Date : 2019-10-31 , DOI: 10.1053/j.gastro.2019.10.028
Aatur D Singhi 1 , Laura D Wood 2 , Emma Parks 3 , Michael S Torbenson 4 , Matthäus Felsenstein 5 , Ralph H Hruban 2 , Marina N Nikiforova 6 , Abigail I Wald 6 , Cihan Kaya 6 , Yuri E Nikiforov 6 , Laura Favazza 6 , Jin He 7 , Kevin McGrath 8 , Kenneth E Fasanella 8 , Randall E Brand 8 , Anne Marie Lennon 9 , Alessandro Furlan 10 , Anil K Dasyam 10 , Amer H Zureikat 11 , Herbert J Zeh 12 , Kenneth Lee 11 , David L Bartlett 11 , Adam Slivka 8
Affiliation  

Background & Aims

Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas and bile duct contain epithelial cells with numerous, large mitochondria and are cystic precursors to pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), respectively. However, IOPNs do not have the genomic alterations found in other pancreatobiliary neoplasms. In fact, no recurrent genomic alterations have been described in IOPNs. PDACs without activating mutations in KRAS contain gene rearrangements, so we investigated whether IOPNs have recurrent fusions in genes.

Methods

We analyzed 20 resected pancreatic IOPNs and 3 resected biliary IOPNs using a broad RNA-based targeted sequencing panel to detect cancer-related fusion genes. Four invasive PDACs and 2 intrahepatic cholangiocarcinomas from the same patients as the IOPNs, were also available for analysis. Samples of pancreatic cyst fluid (n=5, collected before surgery) and bile duct brushings (n=2) were analyzed for translocations. For comparison, we analyzed pancreatobiliary lesions from 126 patients without IOPN (controls).

Results

All IOPNs evaluated were found to have recurring fusions of ATP1B1–PRKACB (n = 13), DNAJB1PRKACA (n = 6), or ATP1B1PRKACA (n = 4). These fusions were also found in corresponding invasive PDACs and intrahepatic cholangiocarcinomas, as well as in matched pancreatic cyst fluid and bile duct brushings. These gene rearrangements were absent from all 126 control pancreatobiliary lesions.

Conclusions

We identified fusions in PRKACA and PRKACB genes in pancreatic and biliary IOPNs, as well as in PDACs and pancreatic cyst fluid and bile duct cells from the same patients. We did not identify these gene fusions in 126 control pancreatobiliary lesions. These fusions might be used to identify patients at risk for IOPNs and their associated invasive carcinomas.



中文翻译:

PRKACA和PRKACB在胰腺和胆管的导管内吞噬乳头状肿瘤中的复发性重排。

背景与目标

胰腺和胆管的导管内吞噬性乳头状瘤(IOPN)包含具有大量线粒体的上皮细胞,分别是胰腺导管腺癌(PDAC)和胆管癌(CCA)的囊性前体。但是,IOPNs在其他胰胆管肿瘤中没有发现基因组改变。实际上,IOPN中没有描述复发的基因组改变。没有激活KRAS突变的PDAC包含基因重排,因此我们研究了IOPNs是否在基因中具有经常性融合。

方法

我们使用广泛的基于RNA的靶向测序小组分析了20个切除的胰腺IOPN和3个切除的胆管IOPN,以检测与癌症相关的融合基因。来自与IOPNs相同的患者的四个浸润性PDAC和2个肝内胆管癌也可用于分析。分析了胰腺囊肿液(n = 5,在手术前收集)和胆管刷牙(n = 2)样品的移位。为了进行比较,我们分析了126例无IOPN的患者(对照)的胰腺胆道病变。

结果

发现评估的所有IOPNs以具有重复融合ATP1B1-PRKACB(N = 13),DNAJB1 - PRKACA(N = 6) ATP1B1 - PRKACA(N = 4)。在相应的浸润性PDAC和肝内胆管癌以及相配的胰腺囊肿液和胆管刷牙中也发现了这些融合。这些基因重排在所有126个对照胰胆管病变中均不存在。

结论

我们在同一患者的胰腺和胆管IOPN中,以及在PDAC和胰腺囊液和胆管细胞中,鉴定了PRKACAPRKACB基因的融合体。我们没有在126个对照胰胆管病变中鉴定出这些基因融合体。这些融合可用于识别有IOPNs及其相关浸润癌风险的患者。

更新日期:2019-11-01
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