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J Pediatr Genet 2019; 08(04): 193-197
DOI: 10.1055/s-0039-1696976
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Genetic Landscape of Mitochondrial Regulatory Region in Pediatric Acute Myeloid Leukemia: Changes from Diagnosis to Relapse

Anudishi Tyagi
1   Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
,
Raja Pramanik
1   Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
,
Radhika Bakhshi
2   Department of Biomedical Science, Shaheed Rajguru College of Applied Sciences, University of Delhi, New Delhi, India
,
Sreenivas Vishnubhatla
3   Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
,
Sameer Bakhshi
1   Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
› Author Affiliations Funding We acknowledge the following funding sources: Department of Biotechnology, Government of India, under grant number BT/PR7197/MED/30/899/2012 (September 26, 2013) and AIIMS, Institutional Junior Research Fellowship grant.
Further Information

Publication History

16 May 2019

05 August 2019

Publication Date:
12 September 2019 (online)

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Abstract

This prospective study aimed to compare the pattern of mitochondrial deoxyribonucleic acid D-loop (mt-DNA D-loop) variations in 41 paired samples of de novo pediatric acute myeloid leukemia (AML) (baseline vs. relapse) patients by Sanger's sequencing. Mean mt-DNA D-loop variation was 10.1 at baseline as compared with 9.4 per patients at relapse. In our study, 28 (68.3%) patients showed change in number of variations from baseline to relapse, 11 (26.8%) patients showed increase, 17 (41.6%) patients showed decrease, and 7 (17.1%) patients who suffered a relapse had a gain at position T489C. No statistically significant difference was observed in the mutation profile of mt-DNA D-loop region from baseline to relapse in the evaluated population of pediatric AML.

Keywords

acute myeloid leukemia - mitochondrial DNA - D-loop - variations - relapse
 

  • References

  • 1 DiMauro S, Schon EA. Mitochondrial DNA mutations in human disease. Am J Med Genet 2001; 106 (01) 18-26
    CrossrefPubMedGoogle Scholar
  • 2 Thorburn DR, Dahl HH. Mitochondrial disorders: genetics, counseling, prenatal diagnosis and reproductive options. Am J Med Genet 2001; 106 (01) 102-114
    CrossrefPubMedGoogle Scholar
  • 3 Anderson S, Bankier AT, Barrell BG. , et al. Sequence and organization of the human mitochondrial genome. Nature 1981; 290 (5806): 457-465
    CrossrefPubMedGoogle Scholar
  • 4 Farrar JE, Schuback HL, Ries RE. , et al. Genomic profiling of pediatric acute myeloid leukemia reveals a changing mutational landscape from disease diagnosis to relapse. Cancer Res 2016; 76 (08) 2197-2205
    CrossrefPubMedGoogle Scholar
  • 5 Riehl LM, Schulte JH, Mulaw MA. , et al. The mitochondrial genetic landscape in neuroblastoma from tumor initiation to relapse. Oncotarget 2016; 7 (06) 6620-6625
    CrossrefPubMedGoogle Scholar
  • 6 Zhou J, Gou H, Ye Y, Zhou Y, Lu X, Ying B. Sequence variations of mitochondrial DNA D-loop region in patients with acute myeloid leukemia. Oncol Lett 2017; 14 (05) 6269-6276
    PubMedGoogle Scholar
  • 7 Tyagi A, Pramanik R, Vishnubhatla S. , et al. Pattern of mitochondrial D-loop variations and their relation with mitochondrial encoded genes in pediatric acute myeloid leukemia. Mutat Res 2018; 810: 13-18
    CrossrefPubMedGoogle Scholar
  • 8 Sharawat SK, Bakhshi R, Vishnubhatla S, Bakhshi S. Mitochondrial D-loop variations in paediatric acute myeloid leukaemia: a potential prognostic marker. Br J Haematol 2010; 149 (03) 391-398
    CrossrefPubMedGoogle Scholar
  • 9 Yu M, Shi Y, Zhang F. , et al. Sequence variations of mitochondrial DNA D-loop region are highly frequent events in familial breast cancer. J Biomed Sci 2008; 15 (04) 535-543
    CrossrefPubMedGoogle Scholar
  • 10 Lièvre A, Blons H, Houllier AM. , et al. Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma. Br J Cancer 2006; 94 (05) 692-697
    CrossrefPubMedGoogle Scholar
  • 11 Tan DJ, Chang J, Chen WL. , et al. Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers. Genes Chromosomes Cancer 2003; 37 (02) 186-194
    CrossrefPubMedGoogle Scholar
  • 12 Pang LJ, Shao JY, Liang XM, Xia YF, Zeng YX. Mitochondrial DNA somatic mutations are frequent in nasopharyngeal carcinoma. Cancer Biol Ther 2008; 7 (02) 198-207
    CrossrefPubMedGoogle Scholar