Identification of somatic mutations using whole-exome sequencing in Korean patients with acute myeloid leukemia

BMC Medical Genetics

Research Article

Hyung-Lae Kim¹  Youngil Koh²  Sung-Soo Yoon²  Ji Wan Park³  Seong Gu Heo⁴  Jong Kwang Kim⁵  Jongsun Jung⁶ 

[1] Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea;Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea;Department of Medical Genetics, College of Medicine, Hallym University, 1 Hallymdaehak-gil, 24252, Chuncheon, Gangwon-do, Republic of Korea;Department of Medical Genetics, College of Medicine, Hallym University, 1 Hallymdaehak-gil, 24252, Chuncheon, Gangwon-do, Republic of Korea;Wide River Institute of Immunology, Seoul National University, Hongcheon, Republic of Korea;Omics Core Lab., National Cancer Center, Goyang, Republic of Korea;The Catholic University, Seoul, Republic of Korea;Syntekabio Inc., Seoul, Republic of Korea;

关键词: Acute myeloid leukemia;    Gene ontology;    Pathway analysis;    Somatic mutation;    Subtype-specific mutation;    Whole-exome sequencing;   

DOI  :  10.1186/s12881-017-0382-y

 received in 2016-01-24, accepted in 2017-02-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAcute myeloid leukemia (AML) is a biologically and clinically heterogeneous cancer of the bone marrow that is characterized by the rapid growth of abnormal myeloid cells.MethodsWe performed a mutational analysis to identify AML somatic mutations using the whole-exome sequencing data of 36 tumor-normal sample pairs from Korean patients with de novo AML. We explored the functional impact of the genes identified in the mutational analyses through an integrated Gene Ontology (GO) and pathway analysis.ResultsA total of 11 genes, including NEFH (p = 6.27 × 10−13 and q = 1.18 × 10−8) and TMPRSS13 (p = 1.40 × 10−10 and q = 1.32 × 10−6), also demonstrated q values less than 0.1 in 36 Korean AML patients. Five out of the 11 novel genes have previously been reported to be associated with other cancers. Two gene mutations, CEBPA (p = 5.22 × 10−5) and ATXN3 (p = 9.75 × 10−4), showed statistical significance exclusively in the M2 and M3 subtypes of the French-American-British classifications, respectively. A total of 501 genes harbored 478 missense, 22 nonsense, 93 frameshift indels, and/or three stop codon deletions and these gene mutations significantly enriched GO terms for signal transduction (GO:0007165, p = 1.77 × 10−3), plasma membrane (GO:0005886, p = 3.07 × 10−4), and scaffold protein binding (GO:0097110, p = 8.65 × 10−4). The mitogen-activated protein kinase (hsa04010, 7.67 × 10−4) was the most enriched Kyoto Encyclopedia of Genes and Genomes pathway.ConclusionsMorphological AML subtypes may in part reflect subtype specific patterns of genomic alterations. Following validation, future studies to evaluate the usefulness of these genes in genetic testing for the early diagnosis and prognostic prediction of AML patients would be worthwhile.

【 授权许可】

CC BY   
© The Author(s). 2017