<abstract xmlns="http://www.w3.org/1999/xhtml">Mutations in mitochondrial tRNA (<italic>mt-tRNA</italic>) genes have been found to be associated with various diseases including lung cancer. To understand the possible relationship between mtRNA mutations and lung cancer, we sequenced the 22 <italic>mt-tRNA</italic> genes from 200 lung cancer blood samples, as well as 100 healthy subjects. As a result, five mutations were identified including the <italic>tRNAAla T5655C, tRNAArg T10454C, tRNALeu(CUN) A12330G, tRNASer(UCN) T7505C</italic> and <italic>tRNAThr G15927A</italic>. These mutations were absent in the healthy subjects. These mutations and polymorphisms were localized at the highly conserved nucleotides of the corresponding mitochondrial tRNAs, which are critical for the tRNA steady state level and may result in failure in the tRNA metabolism. Moreover, through the application of the pathogenicity scoring system, we found that only the T10454C mutation should be classified as a “neutral polymorphism,” while the other mutations were regarded as “definitely pathogenic.” Taken together, our data indicate that <italic>tRNA</italic> genes are the hot-spots for pathogenic mutations associated with lung cancer. Our findings may provide valuable information for pathophysiology, management and genetic counseling of lung cancer.</abstract>

Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with various diseases including lung cancer. To understand the possible relationship between mtRNA mutations and lung cancer, we sequenced the 22 mt-tRNA genes from 200 lung cancer blood samples, as well as 100 healthy subjects. As a result, five mutations were identified including the tRNAAla T5655C, tRNAArg T10454C, tRNALeu(CUN) A12330G, tRNASer(UCN) T7505C and tRNAThr G15927A. These mutations were absent in the healthy subjects. These mutations and polymorphisms were localized at the highly conserved nucleotides of the corresponding mitochondrial tRNAs, which are critical for the tRNA steady state level and may result in failure in the tRNA metabolism. Moreover, through the application of the pathogenicity scoring system, we found that only the T10454C mutation should be classified as a “neutral polymorphism,” while the other mutations were regarded as “definitely pathogenic.” Taken together, our data indicate that tRNA genes are the hot-spots for pathogenic mutations associated with lung cancer. Our findings may provide valuable information for pathophysiology, management and genetic counseling of lung cancer.

Mutational analysis of mitochondrial tRNA genes in patients with lung cancer

Balkan Journal of Medical Genetics

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

{"article-title":"Mutational analysis of mitochondrial tRNA genes in patients with lung cancer"}

Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with various diseases including lung cancer. To understand the possible...

tRNA Species	Sequence Alteration	Location	Conservation Index (%)	Frequency (%)
tRNA^Ala	T5655C	Acceptor arm	100.0	0.5
tRNA^Arg	T10454C	T loop	100.0	1.0
tRNALeu(CUN)	A12330G	Acceptor arm	100.0	1.5
tRNASer(UCN)	T7505C	DHU stem	100.0	0.5
tRNA^Thr	G15927A	Anticodon stem	100.0	2.0

Scoring Criteria	T5655C	Score Score out of 20.	T10454C	Score Score out of 20.	A12330G	Score Score out of 20.	T7505C	Score Score out of 20.	G15927A	Score Score out of 20.	Classification
More than one independent report	yes	2	yes	2	yes	2	yes	2	yes	2	-
Evolutionary conservation of the bp	no changes	2	no changes	2	no changes	2	no changes	2	no changes	2	–
Variant heteroplasmy	no	0	no	0	no	0	no	2	no	2	≤6 points: neutral polymorphisms
Segregation of the mutation with disease	yes	2	yes	2	yes	2	yes	2	yes	2	7-10 points: possibly pathogenic
Histochemical evidence of mt disease	no evidence	0	no	0	yes	2	no	0	no evidence	0	≥ 11 points: definitely pathogenic
Biochemical defect in complexes I, III or IV	no	0	no	0	yes	2	no	0	yes	2	–
Evidence of mutation segregation with biochemical defect from single-fiber studies	no	0	no	0	yes	2	no	0	yes	2	–
Mutant tRNA steady-state level of evidence of pathogenicity in transmt cybrid studies	strong evidence	5	no	0	no	0	strong evidence	5	strong evidence	5	–
Maximum score	definitely pathogenic	Ρ	neutral polymorphism	6	definitely pathogenic	14	definitely pathogenic	11	definitely pathogenic	15

Mutational analysis of mitochondrial tRNA genes in patients with lung cancer

Article Category: Original Article

Publicado en línea: 31 dic 2016

Páginas: 45 - 50

DOI: https://doi.org/10.1515/bjmg-2016-0035

Palabras clave
Lung cancer, Mitochondrial tRNA (mt-tRNA), Mutations, Pathogenic

© 2016 He ZF, Zheng LC, Xie DY, Yu SS, Zhao J

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Characterization of lung cancer associated mt-tRNA mutations.

The pathogenicity scoring system for the mt-tRNA mutations for lung cancer.

Mutational analysis of mitochondrial tRNA genes in patients with lung cancer

Article Category: Original Article

Publicado en línea: 31 dic 2016

Páginas: 45 - 50

DOI: https://doi.org/10.1515/bjmg-2016-0035

Palabras claveLung cancer, Mitochondrial tRNA (mt-tRNA), Mutations, Pathogenic

© 2016 He ZF, Zheng LC, Xie DY, Yu SS, Zhao J

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Characterization of lung cancer associated mt-tRNA mutations.

The pathogenicity scoring system for the mt-tRNA mutations for lung cancer.

Palabras clave
Lung cancer, Mitochondrial tRNA (mt-tRNA), Mutations, Pathogenic