Institute of Pathology, Medical Faculty, Ludwig-Maximilians-University, Thalkirchner Str. 36, 80337, Munich, Germany.
Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
J Cancer Res Clin Oncol. 2018 Nov;144(11):2161-2166. doi: 10.1007/s00432-018-2746-x. Epub 2018 Sep 7.
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, lacking relevant prognostic and predictive biomarkers. DNA polymerase epsilon (POLE) has important functions in the maintenance of genetic stability during DNA replication and has previously been associated with favorable prognosis in endometrial and colorectal cancer. However, its relevance in advanced pancreatic cancer (aPDAC) has not been examined to date.
Using pyrosequencing on tumoral DNA extracted from 60 samples from the AIO-PK0104 study as well as 55 samples from completed translational trials, we examined POLE hotspot mutations in exon 9 (P286R) and exon 13 (V411R/L/M) in the POLE gene exonuclease domain. DNA extracted from 37 endometrial carcinomas were tested as positive controls. Publically available sequencing databases were searched for POLE mutations in PDAC samples.
Fifty-three patients (pts) were men, 62 pts were women, median age was 61.2 years. Median overall survival (OS) was 7.4 months and median progression free survival (PFS) was 4.0 months. In four of the 37 endometrial carcinomas POLE mutations were detected in exon 9 (10.8%) and none in exon 13. In none of the overall 115 aPDAC tumors POLE gene hotspot mutations could be detected.
Mutations in the hotspot regions of exon 9 and 13 of the POLE gene are very rare events in advanced pancreatic cancer. Thus, it is unlikely that POLE gene mutations contribute to genetic instability in the vast majority of aPDAC. POLE mutation does not serve as a relevant biomarker and should not be tested on a regular basis in PDAC.
胰腺导管腺癌（PDAC）是一种破坏性疾病，缺乏相关的预后和预测生物标志物。DNA 聚合酶 epsilon（POLE）在 DNA 复制过程中维持遗传稳定性方面具有重要功能，先前与子宫内膜癌和结直肠癌的良好预后相关。然而，迄今为止，其在晚期胰腺腺癌（aPDAC）中的相关性尚未得到检验。
使用焦磷酸测序技术对 AIO-PK0104 研究中 60 个样本的肿瘤 DNA 以及 55 个已完成的转化试验样本进行检测，我们在 POLE 基因外切酶结构域的exon 9（P286R）和 exon 13（V411R/L/M）中检测 POLE 热点突变。从 37 例子宫内膜癌中提取的 DNA 作为阳性对照进行检测。在 PDAC 样本中搜索公共可用的测序数据库中 POLE 突变。
53 名患者（pts）为男性，62 名患者为女性，中位年龄为 61.2 岁。中位总生存期（OS）为 7.4 个月，中位无进展生存期（PFS）为 4.0 个月。在 37 例子宫内膜癌中，有 4 例检测到 exon 9 中的 POLE 突变（10.8%），而 exon 13 中没有突变。在总共 115 例晚期胰腺腺癌肿瘤中均未检测到 POLE 基因热点突变。
POLE 基因 exon 9 和 13 热点区域的突变在晚期胰腺腺癌中非常罕见。因此，POLE 基因突变不太可能导致绝大多数 aPDAC 中的遗传不稳定性。POLE 突变不能作为相关的生物标志物，不应在 PDAC 中常规进行检测。
