Novel Mutations in the Displacement Loop of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia: A Genetic Sequencing Study

作者：Yacoub Haitham Ahmed^*; Mahmoud Wael Mahmoud; El Baz Hatim Alaa El Din; Eid Ola Mohamed; ELfayoumi Refaat Ibrahim; Elhamidy Salem Mohamed; Mahmoud Maged M

来源：Asian Pacific Journal of Cancer Prevention, 2014, 15(21): 9283-9289.

DOI：10.7314/APJCP.2014.15.21.9283

• Acute lymphoblastic leukemia
• D-loop
• mtDNA
• mutations
• genetic sequencing

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Materials and Methods: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. Results: This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. Conclusions: Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.

• 出版日期2014