Implications of mitochondrial DNA variants in pediatric B-cell acute lymphoblastic leukemia

Egyptian Journal of Medical Human Genetics - Tập 23 Số 1
Ayushi Jain1, Amit Katiyar2, Ritika Singh1, Sameer Bakhshi3, Harpreet Singh2, Jayanth Kumar Palanichamy1, Archna Singh1
1Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India
2Division of Biomedical Informatics, ICMR-AIIMS Computational Genomics Centre, Indian Council of Medical Research (ICMR), Ansari Nagar, New Delhi, 110029, India
3Department of Medical Oncology, B.R.A.I.R.C.H., All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, 110029, India

Tóm tắt

Abstract Background Research on the role of variations in the mitochondrial genome in pathogenesis of acute lymphoblastic leukemia (ALL) has been unfolding at a rapid rate. Our laboratory has previously described higher number of copies of the mitochondrial genomes per cell in pediatric ALL patients as compared to the healthy controls. In the current study, we evaluated the pattern of mitochondrial genome variations in 20 de-novo pediatric B-ALL cases and seven controls. Quantitative real-time Polymerase Chain Reaction was used for estimation of mitochondrial genomes’ copy number in bone marrow samples of each ALL patient and peripheral blood samples of controls. The complete mitochondrial genomes of all samples were sequenced using the Illumina platform. Results Sequencing data analysis using multiple mitochondrial genome databases revealed 325 variants in all 27 samples, out of which 221 variants were previously known while 104 were unassigned, new variants. The 325 variants consisted of 7 loss-of-function variants, 131 synonymous variants, 75 missense variants, and 112 non-coding variants. New, missense variants (n = 21) were identified in genes encoding the electron transport chain complexes with most of them encoding ND4, ND5 of complex I. Missense and loss-of-function variants were found to be deleterious by many predictor databases of pathogenicity. MuTect2 identified true somatic variants present only in tumors between patient-sibling pairs and showed overlap with missense and loss-of-function variants. Online MtDNA-server showed heteroplasmic and homoplasmic variants in mitochondrial genome. Conclusions The data suggest that some of these variations might have a deleterious impact on the expression of mitochondrial encoded genes with a possible functional relevance in leukemia.

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Egyptian Journal of Medical Human Genetics

Tập 23 Số 1

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