High frequency of mitochondrial DNA D-loop mutations in Ewing's sarcoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Somatic mutations and polymorphisms in mitochondrial DNA (mtDNA) D-loop are implicated in various human cancers.
• Ewing sarcoma (EWS) is a rare malignancy with an unknown specific carcinogenic pathway.

Purpose of the Study:

• To investigate the presence of genetic alterations in the mtDNA D-loop region of EWS.
• To explore the potential association between mtDNA D-loop mutations and EWS carcinogenesis.

Main Methods:

• Direct DNA sequencing was used to analyze complete mtDNA D-loop sequences.
• 17 pairs of EWS tumor tissues and corresponding peripheral blood samples were compared.
• Germline polymorphisms in the D-loop were also screened.

Main Results:

• 19 somatic mutations (substitutions, insertions, deletions) were identified in 12 out of 17 (70.6%) EWS tumor specimens.
• 40 germline polymorphisms, including one novel variant, were found in the D-loop.
• Mutations and variations were predominantly located in hypervariable segments (HVS1, HVS2) and a homopolymeric C stretch.

Conclusions:

• This study reports a high frequency of mtDNA D-loop mutations in EWS for the first time.
• mtDNA alterations are potentially involved in the initiation and/or progression of EWS.
• No significant correlation was found between mtDNA D-loop mutations and EWS clinicopathological factors.