targeted sequencing

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

/ CY Liu / 發表迴響

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.

9. Deciphering Genetic Alterations of Taiwanese Patients with Pancreatic Adenocarcinoma through Targeted Sequencing (參考著作)下載

Targeted Sequencing of Taiwanese Breast Cancer with Risk Stratification by the Concurrent Genes Signature: A Feasibility Study

/ CY Liu / 發表迴響

Ching-Shui Huang 1 2, Chih-Yi Liu 3, Tzu-Pin Lu 4, Chi-Jung Huang 5 6, Jen-Hwey Chiu 7 8, Ling-Ming Tseng 8 9, Chi-Cheng Huang 9 10

Affiliations
  1. Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei 106, Taiwan.
  2. School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  3. Department of Pathology, Cathay General Hospital Sijhih, New Taipei 221, Taiwan.
  4. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei 110, Taiwan.
  5. Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan.
  6. National Defense Medical Center, Department of Biochemistry, Taipei 114, Taiwan.
  7. Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11121, Taiwan.
  8. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
  9. Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 1121, Taiwan.
  10. School of Public Health, College of Public Health, National Taiwan University, Taipei 100, Taiwan.

ABSTRACT

Breast cancer is the most common female malignancy in Taiwan, while conventional clinical and pathological factors fail to provide full explanation for prognostic heterogeneity. The aim of the study was to evaluate the feasibility of targeted sequencing combined with concurrent genes signature to identify somatic mutations with clinical significance. The extended concurrent genes signature was based on the coherent patterns between genomic and transcriptional alterations. Targeted sequencing of 61 Taiwanese breast cancers revealed 1036 variants, including 76 pathogenic and 545 likely pathogenic variants based on the ACMG classification. The most frequently mutated genes were NOTCH, BRCA1, AR, ERBB2, FANCA, ATM, and BRCA2 and the most common pathogenic deletions were FGFR1, ATM, and WT1, while BRCA1 (rs1799965), FGFR2 (missense), and BRCA1 (rs1799949) were recurrent pathogenic SNPs. In addition, 38 breast cancers were predicted into 12 high-risk and 26 low-risk cases based on the extended concurrent genes signature, while the pathogenic PIK3CA variant (rs121913279) was significantly mutated between groups. Two deleterious SH3GLB2 mutations were further revealed by multivariate Cox’s regression (hazard ratios: 29.4 and 16.1). In addition, we identified several significantly mutated or pathogenic variants associated with differentially expressed signature genes. The feasibility of targeted sequencing in combination with concurrent genes risk stratification was ascertained. Future study to validate clinical applicability and evaluate potential actionability for Taiwanese breast cancers should be initiated.

Keywords: Taiwan; actionable mutations; breast cancer; concurrent genes; risk stratification; targeted sequencing.

>J Pers Med. 2021 Jun 28;11(7):613. doi: 10.3390/jpm11070613.

4. Targeted Sequencing of Taiwanese Breast Cancer with Risk Stratification (參考著作)下載