Open Access

Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer

H.J. Ding
H.J. Ding
, 
Y.P. Zhao
Y.P. Zhao
, 
Z.C. Jiang
Z.C. Jiang
, 
D.T. Zhou
D.T. Zhou
 and 
R. Zhu
R. Zhu
   | May 02, 2023
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Article Category: ORIGINAL ARTICLE
Published Online: May 02, 2023
Page range: 15 - 22
DOI: https://doi.org/10.2478/bjmg-2022-0020
Keywords
© 2022 Ding H.J. et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1.

Cloverleaf structures of five mt-tRNAs. Arrows indicate the locations of breast cancer-associated mt-tRNA mutations.
Cloverleaf structures of five mt-tRNAs. Arrows indicate the locations of breast cancer-associated mt-tRNA mutations.

Figure 2.

Analysis of mitochondrial functions. A. mtDNA copy number analysis in patients with and without mt-tRNA mutations. B. ATP qualification in patients with and without mt-tRNA mutations.
Analysis of mitochondrial functions. A. mtDNA copy number analysis in patients with and without mt-tRNA mutations. B. ATP qualification in patients with and without mt-tRNA mutations.

Summary of clinico-pathological characteristics of breast cancer patients

Characteristics Data (mean ± SD or n (frequency in %))
Gender
    Male 2 (2.5)
    Female 78 (97.5)
Age
    >50 years 45 (56.25)
    ≤50 years 35 (43.75)
Body mass index (kg/m2) 25.4±3.3
Histological grade
    I 15 (18.75)
    II 28 (35)
    III 37 (46.25)
TNM stage
    I 10 (12.5)
    II 13 (16.25)
    III 19 (23.75)
    IV 38 (47.5)
Cancer metastasis
    Positive 38 (47.5)
    Negative 42 (52.5)

mt-tRNA mutations identified in this case-control study

Gene Sequence alternation CI (%)a Homoplasmy /Heteroplasmy Watson-Crick base pairingb Nucleotide at tRNA Location Number of 80 breast cancer tissues (%) Number of 80 matched normal adjacent tissues (%) mtDNA haplogroup Disease association
tRNAVal G1606A 100 Heteroplasmy G-C↓ 5 Acceptor arm 1 (1.25) 0 N9a Progressive ataxia, seizures, mental deterioration, mild myopathy, and hearing loss
tRNAIle A4300G 100 Heteroplasmy C-G↓ 42 Anticodon stem 1 (1.25) 0 C4c Cardiomyopathy
tRNASer(UCN) T7505C 100 Homoplasmy A-T↓ 10 D-arm 2 (2.5) 0 F1 Deafness
tRNAGlu A14693G 100 Homoplasmy 54 TΨC-loop 2 (2.5) 0 Y2 MELAS, deafness, LHON
tRNAThr G15927A 100 Homoplasmy C-G↓ 42 Anticodon stem 1 (1.25) 0 B5b Parkinson’s disease, LHON, deafness, CHD,

The predicted pathogenicity of breast cancer-associated mt-tRNA mutations

Scoring criteria G1606A mutation Score A4300G mutation Score T7505C mutation Score A14693G mutation Score G15927A mutation Score Classification
More than one independent report Yes 2 Yes 2 Yes 2 Yes 2 Yes 2 ≤6 points: neutral polymorphisms;
Evolutionary conservation of the base pair No change 2 No change 2 No change 2 No change 2 No change 2 7~10 points: possibly pathogenic;
Variant heteroplasmy No 0 No 0 No 0 No 0 No 0
Segregation of the mutation with disease Yes 2 No 0 Yes 2 Yes 2 Yes 2 11-13 points (not including evidence from single fiber, steady-state level or trans-mitochondrial cybrid studies): probably pathogenic
Histochemical evidence of mitochondrial disease No evidence 0 No evidence 0 No evidence 0 No evidence 0 No evidence 0
Biochemical defect in complex I, III or IV Yes 2 Yes 2 Yes 2 No 0 Yes 2
Evidence of mutation segregation with biochemical defect from single-fiber studies No 0 No 0 No 0 No 0 No 0
Mutant mt-tRNA steady-state level or evidence of pathogenicity in trans-mitochondrial cybrid studies Strong evidence 5 Strong evidence 5 Strong evidence 5 Weak evidence 3 Strong evidence 5 ≥11 points (including evidence from single fiber, steady-state level or trans-mitochondrial cybrid studies): definitely pathogenic
Maximum score Definitely pathogenic 13 Definitely pathogenic 11 Definitely pathogenic 13 Possibly pathogenic 9 Definitely pathogenic 13
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Language:
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