TET2 mutations in acute myeloid leukemia: a comprehensive study in patients of Sindh, Pakistan

PeerJ

article

Abdul Rehman Khalil Shaikh¹  Ikram Ujjan¹  Muhammad Irfan²  Arshi Naz¹  Tahir Shamsi³  Muhammad Tariq Masood Khan⁴  Muhammad Shakeel² 

[1] Department of Pathology, Liaquat University of Medical & Health Sciences Jamshoro;Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine & Drug Research, University of Karachi;National Institute of Blood Disease & Bone Marrow Transplantation;Department of Hematology, Northwest School of Medicine

关键词: AML;    TET2;    PCR;    DNA methylation;    Cancer genetics;    Coding exons;    Frameshift mutations;   

DOI  :  10.7717/peerj.10678

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background The tet oncogene family member 2 (TET2) gene has been reported to be involved in DNA methylation and epigenetic regulation in acute myeloid leukemia (AML). Various studies have proven functional role of TET2 mutations in AML. We herein studied the frequency and genotype-phenotype correlation of TET2 gene in AML patients in Sindh, Pakistan. Patients and methods The current study was carried out at Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan, in collaboration with National Institute of Blood Disease & Bone Marrow Transplant, Karachi, Pakistan, during the period from June 2019 to June 2020. A total of 130 patients diagnosed with AML were screened for TET2 mutations. Whole exome sequencing of 14 individuals was carried out to find the genetic variants in TET2 gene. The pathogenicity of the variants was predicted by SIFT, PolyPhen2, Mutation Taster and CADD Phred scores. The allele frequency of the variants was compared with global population using 1000 genomes project and Exome Aggregation Consortium (ExAC). Furthermore, exon 3 and exon 5 of the TET2 gene were sequenced by using Sanger sequencing. The findings were correlated with subtypes of AML and corresponding karyotypes. Results G identified in the TET2 gene. Majority of the exon 3 mutations were seen in the patients diagnosed with AML with maturation, and had a normal karyotype. Conclusion TET2 mutations were identified in around 16% of the total patients of our study indicating other mechanisms being involved in pathophysiology of AML in this cohort. The TET2 mutations provide a prognostic value in determining AML classification.

【 授权许可】

CC BY