Yi Fang1,2, Xiao Ma3, Jing Zeng2, Yanwen Jin1, Yong Hu1, Jinjing Wang2, Ran Liu2, Cheng Cao1. 1. Beijing Institute of Biotechnology, Beijing, China. 2. Endocrinology Department, 307 hospital, PLA, Beijing, China. 3. Key Laboratory of Carcinogenesis and Translational Research, Department of Head and Neck, Perking University Cancer Hospital and Institute, Beijing, China.
Abstract
BACKGROUND/AIMS: The purpose of the study was to investigate the altered driver genes and signal pathways during progression of papillary thyroid cancer (PTC) via next-generation sequencing technology. METHODS: The DNA samples for whole exome sequencing (WES) analyses were extracted from 11 PTC tissues and adjacent normal tissues samples. Direct Sanger sequencing was applied to validate the identified mutations. RESULTS: Among the 11 pairs of tissues specimens, 299 single nucleotide variants (SNVs) in 75 genes were identified. The most common pattern of base pair substitutions was T:A>C:G (49.83%), followed by C:G>T:A (18.06%) and C:G>G:C (15.05%). The altered genes were mainly implicated in MAPK (mitogen-activated protein kinase), PPAR (peroxisome proliferator-activated receptors), and p53 signaling pathways. In addition, 12 novel identified driver genes were validated by Sanger sequencing. The mutations of FAM133A, DPCR1, JAK1, C10orf10, EPB41L3, GPRASP1 and IWS1 exhibited in multiple PTC cases. Furthermore, the PTC cases exhibited individual mutational signature, even the same gene might present different mutational status in different cases. CONCLUSION: Multiple PTC-related somatic mutations and signal pathways are identified via WES and Sanger sequencing methods. The novel identified mutations in genes such as FAM133A, DPCR1, and JAK1 may be potential therapeutic targets for PTC patients.
BACKGROUND/AIMS: The purpose of the study was to investigate the altered driver genes and signal pathways during progression of papillary thyroid cancer (PTC) via next-generation sequencing technology. METHODS: The DNA samples for whole exome sequencing (WES) analyses were extracted from 11 PTC tissues and adjacent normal tissues samples. Direct Sanger sequencing was applied to validate the identified mutations. RESULTS: Among the 11 pairs of tissues specimens, 299 single nucleotide variants (SNVs) in 75 genes were identified. The most common pattern of base pair substitutions was T:A>C:G (49.83%), followed by C:G>T:A (18.06%) and C:G>G:C (15.05%). The altered genes were mainly implicated in MAPK (mitogen-activated protein kinase), PPAR (peroxisome proliferator-activated receptors), and p53 signaling pathways. In addition, 12 novel identified driver genes were validated by Sanger sequencing. The mutations of FAM133A, DPCR1, JAK1, C10orf10, EPB41L3, GPRASP1 and IWS1 exhibited in multiple PTC cases. Furthermore, the PTC cases exhibited individual mutational signature, even the same gene might present different mutational status in different cases. CONCLUSION: Multiple PTC-related somatic mutations and signal pathways are identified via WES and Sanger sequencing methods. The novel identified mutations in genes such as FAM133A, DPCR1, and JAK1 may be potential therapeutic targets for PTC patients.
Authors: Tariq Masoodi; Abdul K Siraj; Sarah Siraj; Saud Azam; Zeeshan Qadri; Sandeep K Parvathareddy; Saif S Al-Sobhi; Mohammed AlDawish; Fowzan S Alkuraya; Khawla S Al-Kuraya Journal: Am J Hum Genet Date: 2019-10-24 Impact factor: 11.025