Spectrum of gene mutations identified by targeted next-generation sequencing in Chinese leukemia patients

Autor: Hong-Xia Yao, Xiangjun Fu, Yueqing Chen, Wen-Ting Chen, Yanping Pan, Gu-Yun Wang, Yipeng Ding, Cong-Ming Wu, Li Guo
Rok vydání: 2019
Předmět:
0301 basic medicine
Adult
Male
Myeloid leukocyte differentiation
INDELs
lcsh:QH426-470
Genomics
030105 genetics & heredity
Biology
Gene mutation
medicine.disease_cause
Polymorphism
Single Nucleotide
DNA sequencing
03 medical and health sciences
INDEL Mutation
hemic and lymphatic diseases
Proto-Oncogene Proteins
Genetics
medicine
Humans
Receptor
Notch2
Molecular Biology
Genetics (clinical)
Adaptor Proteins
Signal Transducing
Aged
Mutation
Leukemia
Fanconi Anemia Complementation Group A Protein
breakpoint cluster region
High-Throughput Nucleotide Sequencing
Sequence Analysis
DNA
Original Articles
Middle Aged
Protein-Tyrosine Kinases
medicine.disease
FANCA
pathway analysis
lcsh:Genetics
Cytoskeletal Proteins
030104 developmental biology
Genetic Loci
Proto-Oncogene Proteins c-bcr
gene ontology
Female
Original Article
SNVs
Zdroj: Molecular Genetics & Genomic Medicine
Molecular Genetics & Genomic Medicine, Vol 8, Iss 9, Pp n/a-n/a (2020)
ISSN: 2324-9269
Popis: Background Despite targeted sequencing have identified several mutations for leukemia, there is still a limit of mutation screening for Chinese leukemia. Here, we used targeted next‐generation sequencing for testing the mutation patterns of Chinese leukemia patients. Methods We performed targeted sequencing of 504 tumor‐related genes in 109 leukemia samples to identify single‐nucleotide variants (SNVs) and insertions and deletions (INDELs). Pathogenic variants were assessed based on the American College of Medical Genetics and Genomics (ACMG) guidelines. The functional impact of pathogenic genes was explored through gene ontology (GO), pathway analysis, and protein–protein interaction network in silico. Results We identified a total of 4,655 SNVs and 614 INDELs in 419 genes, in which PDE4DIP, NOTCH2, FANCA, BCR, and ROS1 emerged as the highly mutated genes. Of note, we were the first to demonstrate an association of PDE4DIP mutation and leukemia. Based on ACMG guidelines, 39 pathogenic and likely pathogenic mutations in 27 genes were found. GO annotation showed that the biological process including gland development, leukocyte differentiation, respiratory system development, myeloid leukocyte differentiation, mesenchymal to epithelial transition, and so on were involved. Conclusion Our study provided a map of gene mutations in Chinese patients with leukemia and gave insights into the molecular pathogenesis of leukemia.
We identified a total of 4,655 single‐nucleotide variants and 614 insertions and deletions in 419 genes, in which PDE4DIP, NOTCH2, FANCA, BCR and ROS1 emerged as the highly mutated genes. Based on American College of Medical Genetics and Genomics guidelines, 39 pathogenic and likely pathogenic mutations in 27 genes were found. Our study provided a map of gene mutations in Chinese patients with leukemia and gave insights into the molecular pathogenesis of leukemia.
Databáze: OpenAIRE
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