Background: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed late, with an extremely poor prognosis. Treatment options like surgery, radiation, and chemotherapy are rarely curative. Tumor progression from primary to metastatic PDAC remains poorly understood at the molecular level. Methods: In the current study, we analyzed the molecular profiles of metastatic PDAC obtained via the Oncomine Comprehensive Assay in comparison to primary PDAC. Results: The current study cohort consisted of 115 metastatic PDAC cases, of which 71 (62%) cases succeeded in molecular testing while the remaining 44 (38%) cases contained insufficient tumor cells. Molecular profiling of 71 cases revealed a total of 239 molecular alterations, 3.4 alterations per case on average, predominantly in the form of gene mutations. The most common gene mutations includedKRAS(86%) andTP53(83%) mutations. Gene copy number alterations were also detected in 19 (27%) cases involving genes such asCCNE1andERBB2. Compared to the molecular profiles of primary PDAC reported in our prior study and TCGA database, there seemed to be increased rates ofTP53,ARID1A,BRAF, andPIK3CAmutations in the metastatic diseases. Conclusions: These findings suggest that metastatic PDAC possesses unique genetic characteristics, offering potential therapeutic targets in advanced-stage pancreatic cancer.
背景：胰腺导管腺癌（PDAC）通常诊断较晚，预后极差。手术、放疗和化疗等治疗手段很少能实现根治。从原发性PDAC到转移性PDAC的肿瘤进展在分子水平上仍知之甚少。方法：本研究通过Oncomine综合检测分析了转移性PDAC的分子特征，并与原发性PDAC进行了比较。结果：本研究队列包括115例转移性PDAC病例，其中71例（62%）成功完成分子检测，其余44例（38%）因肿瘤细胞不足未能检测。对71例病例的分子谱分析共发现239处分子改变，平均每例3.4处，主要表现为基因突变。最常见的基因突变包括KRAS（86%）和TP53（83%）突变。此外，在19例（27%）病例中检测到基因拷贝数改变，涉及CCNE1和ERBB2等基因。与我们先前研究及TCGA数据库中报道的原发性PDAC分子谱相比，转移性病变中TP53、ARID1A、BRAF和PIK3CA的突变率似乎有所增加。结论：这些发现表明转移性PDAC具有独特的遗传特征，为晚期胰腺癌提供了潜在的治疗靶点。
Comprehensive Molecular Profiling of Metastatic Pancreatic Adenocarcinomas
肿瘤(癌症)患者之家