Junliang Lu1, Ruoying Yu2, Rui Liu2, Xiaolong Liang3, Jian Sun1, Hui Zhang1, Huanwen Wu1, Zhiwen Zhang1, Yang W Shao4,5, Junchao Guo6, Zhiyong Liang1. 1. Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. 2. Translational Medicine Research Institute, Geneseeq Technology Inc, Toronto, ON, Canada. 3. Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. 4. Nanjing Geneseeq Technology Inc, Nanjing, Canada. 5. School of Public Health, Nanjing Medical University, Nanjing, China. 6. Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Abstract
OBJECTIVES: Pancreatic cancer (PC) is one of the most lethal malignancies with an increasing death rate over the years. We performed targeted sequencing and survival analyses on 90 Chinese pancreatic cancer patients, hoping to identify genomic biomarkers associated with clinical outcomes and therapeutic options. METHOD: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens of 90 pancreatic cancer patients and sequenced. The associations with clinicopathological factors were analyzed. RESULT: High prevalence of driver mutations in KRAS, TP53, CDKN2A, SMAD4, and ARID1A genes were found. Most mutated genes in PC belonged to cell cycle and DNA damage repair pathways. Tumors that arise from the pancreas' body and tail (BT tumors) displayed a higher ratio of mutated KRAS and TP53 than those that arise from the pancreas' head and neck (HN tumors), who showed less diverse KRAS subtypes. Patients with a KRAS p.G12R mutated tumor tended to have a prolonged disease-free survival (DFS) and overall survival (OS) than other KRAS subtypes. Those with an altered ARID1A gene and more than two mutated driver genes tended to have a shorter DFS and OS. CONCLUSION: HN and BT tumors of the pancreas displayed different mutational profiles, which had prognostic significances and indicated different potential therapeutic options.
OBJECTIVES:Pancreatic cancer (PC) is one of the most lethal malignancies with an increasing death rate over the years. We performed targeted sequencing and survival analyses on 90 Chinese pancreatic cancerpatients, hoping to identify genomic biomarkers associated with clinical outcomes and therapeutic options. METHOD: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens of 90 pancreatic cancerpatients and sequenced. The associations with clinicopathological factors were analyzed. RESULT: High prevalence of driver mutations in KRAS, TP53, CDKN2A, SMAD4, and ARID1A genes were found. Most mutated genes in PC belonged to cell cycle and DNA damage repair pathways. Tumors that arise from the pancreas' body and tail (BT tumors) displayed a higher ratio of mutated KRAS and TP53 than those that arise from the pancreas' head and neck (HN tumors), who showed less diverse KRAS subtypes. Patients with a KRAS p.G12R mutated tumor tended to have a prolonged disease-free survival (DFS) and overall survival (OS) than other KRAS subtypes. Those with an altered ARID1A gene and more than two mutated driver genes tended to have a shorter DFS and OS. CONCLUSION: HN and BT tumors of the pancreas displayed different mutational profiles, which had prognostic significances and indicated different potential therapeutic options.
Keywords:
DNA Damage Repair pathway; KRAS subtype; body and tail of pancreas; disease-free survival; head and neck of pancreas; overall survival; pancreatic cancer
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