Dataset Information

Mutational profiling of mitochondrial DNA reveals an epithelial ovarian cancer-specific evolutionary pattern contributing to high oxidative metabolism.

ABSTRACT:

Background

Epithelial ovarian cancer (EOC) heavily relies on oxidative phosphorylation (OXPHOS) and exhibits distinct mitochondrial metabolic reprogramming. Up to now, the evolutionary pattern of somatic mitochondrial DNA (mtDNA) mutations in EOC tissues and their potential roles in metabolic remodelling have not been systematically elucidated.

Methods

Based on a large somatic mtDNA mutation dataset from private and public EOC cohorts (239 and 118 patients, respectively), we most comprehensively characterised the EOC-specific evolutionary pattern of mtDNA mutations and investigated its biological implication.

Results

Mutational profiling revealed that the mitochondrial genome of EOC tissues was highly unstable compared with non-cancerous ovary tissues. Furthermore, our data indicated the delayed heteroplasmy accumulation of mtDNA control region (mtCTR) mutations and near-complete absence of mtCTR non-hypervariable segment (non-HVS) mutations in EOC tissues, which is consistent with stringent negative selection against mtCTR mutation. Additionally, we observed a bidirectional and region-specific evolutionary pattern of mtDNA coding region mutations, manifested as significant negative selection against mutations in complex V (ATP6/ATP8) and tRNA loop regions, and potential positive selection on mutations in complex III (MT-CYB). Meanwhile, EOC tissues showed higher mitochondrial biogenesis compared with non-cancerous ovary tissues. Further analysis revealed the significant association between mtDNA mutations and both mitochondrial biogenesis and overall survival of EOC patients.

Conclusions

Our study presents a comprehensive delineation of EOC-specific evolutionary patterns of mtDNA mutations that aligned well with the specific mitochondrial metabolic remodelling, conferring novel insights into the functional roles of mtDNA mutations in EOC tumourigenesis and progression.

SUBMITTER: Xie F

PROVIDER: S-EPMC10775184 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Mutational profiling of mitochondrial DNA reveals an epithelial ovarian cancer-specific evolutionary pattern contributing to high oxidative metabolism.

Xie Fanfan F Guo Wenjie W Wang Xingguo X Zhou Kaixiang K Guo Shanshan S Liu Yang Y Sun Tianlei T Li Shengjing S Xu Zhiyang Z Yuan Qing Q Zhang Huanqin H Gu Xiwen X Xing Jinliang J Liu Shujuan S

Clinical and translational medicine 20240101 1

<h4>Background</h4>Epithelial ovarian cancer (EOC) heavily relies on oxidative phosphorylation (OXPHOS) and exhibits distinct mitochondrial metabolic reprogramming. Up to now, the evolutionary pattern of somatic mitochondrial DNA (mtDNA) mutations in EOC tissues and their potential roles in metabolic remodelling have not been systematically elucidated.<h4>Methods</h4>Based on a large somatic mtDNA mutation dataset from private and public EOC cohorts (239 and 118 patients, respectively), we most ...[more]

PMID: 38193640

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Dataset Information

Mutational profiling of mitochondrial DNA reveals an epithelial ovarian cancer-specific evolutionary pattern contributing to high oxidative metabolism.

Background

Methods

Results

Conclusions

Publications

Mutational profiling of mitochondrial DNA reveals an epithelial ovarian cancer-specific evolutionary pattern contributing to high oxidative metabolism.

Similar Datasets

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