Deciphering Genetic Alterations of Taiwanese Patients with Pancreatic Adenocarcinoma through Targeted Sequencing

/ CY Liu

Chi-Cheng Huang 1 2 3, Chih-Yi Liu 4, Chi-Jung Huang 5 6, Yao-Chun Hsu 7, Heng-Hui Lien 8 9, Jia-Uei Wong 10, Feng-Chuan Tai 8, Wen-Hui Ku 11, Chi-Feng Hung 9, Jaw-Town Lin 12, Ching-Shui Huang 8 13, Han-Sun Chiang 9

Affiliations
  1. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
  2. Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
  3. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
  4. Department of Pathology, Cathay General Hospital SiJhih, New Taipei 221, Taiwan.
  5. Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan.
  6. Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.
  7. Division of Gastroenterology, Department of Internal Medicine, E-da Hospital, Kaohsiung 82445, Taiwan.
  8. Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei 106, Taiwan.
  9. School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei 242, Taiwan.
  10. Division of General Surgery, Department of Surgery, Fu-Jen Catholic University Hospital, New Taipei 243, Taiwan.
  11. Department of Clinical Pathology and Molecular Medicine, Taipei Institute of Pathology, Taipei 10374, Taiwan.
  12. Digestive Medicine Center, China Medical University Hospital, Taichung 404, Taiwan.
  13. School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

ABSTRACT

Pancreatic adenocarcinoma (PAC) is the 8th leading cause of cancer-related deaths in Taiwan, and its incidence is increasing. The development of PAC involves successive accumulation of multiple genetic alterations. Understanding the molecular pathogenesis and heterogeneity of PAC may facilitate personalized treatment for PAC and identify therapeutic agents. We performed tumor-only next-generation sequencing (NGS) with targeted panels to explore the molecular changes underlying PAC patients in Taiwan. The Ion Torrent Oncomine Comprehensive Panel (OCP) was used for PAC metastatic lesions, and more PAC samples were sequenced with the Ion AmpliSeq Cancer Hot Spot (CHP) v2 panel. Five formalin-fixed paraffin-embedded (FFPE) metastatic PAC specimens were successfully assayed with OCP, and KRAS was the most prevalent alteration, which might contraindicate the use of anti-EGFR therapy. One PAC patient harbored a FGFR2 p. C382R mutation, which might benefit from FGFR tyrosine kinase inhibitors. An additional 38 samples assayed with CHP v2 showed 100 hotspot variants, collapsing to 54 COSMID IDs. The most frequently mutated genes were TP53, KRAS, and PDGFRA (29, 23, 10 hotspot variants), impacting 11, 23, and 10 PAC patients. Highly pathogenic variants, including COSM22413 (PDGFRA, FATHMM predicted score: 0.88), COSM520, COSM521, and COSM518 (KRAS, FATHMM predicted score: 0.98), were reported. By using NGS with targeted panels, somatic mutations with therapeutic potential were identified. The combination of clinical and genetic information is useful for decision making and precise selection of targeted medicine.

Keywords: Taiwan; actionable mutation; next-generation sequencing; pancreatic adenocarcinoma; targeted sequencing.

>Int J Mol Sci. 2022 Jan 29;23(3):1579. doi: 10.3390/ijms23031579.

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