Somatic mutations in the D‐loop of mitochondrial DNA in head and neck squamous cell carcinoma

Liu, Shih–An; Jiang, Rong–San; Wang, Wenyi; Lin, Jin‐Ching

doi:10.1002/hed.23680

Cited by 11 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, two groups [ 17 , 18 ] reported that most of missense mutations of mtDNA do not have distinct physiological advantages, indicating that these mutations are not under positive selection. In addition, several studies also concluded that mtDNA mutations are not related to the developments of most cases of lung cancer [ 19 ] and head and neck squamous cell carcinoma [ 20 ]. All of these lines of evidence seem to be contradictory to the critical roles of mtDNA mutations in tumor development, leaving unclear whether somatic mtDNA mutations are drivers, or just bystanders, of tumor development.…”

Section: Introductionmentioning

confidence: 99%

Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations

Guo

et al. 2017

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundPrevious studies have indicated that tumor mitochondrial DNA (mtDNA) mutations are primarily shaped by relaxed negative selection, which is contradictory to the critical roles of mtDNA mutations in tumorigenesis. Therefore, we hypothesized that site-specific selection may influence tumor mtDNA mutations.MethodsTo test our hypothesis, we developed the largest collection of tumor mtDNA mutations to date and evaluated how natural selection shaped mtDNA mutation patterns. ResultsOur data demonstrated that both positive and negative selections acted on specific positions or functional units of tumor mtDNAs, although the landscape of these mutations was consistent with the relaxation of negative selection. In particular, mutation rate (mutation number in a region/region bp length) in complex V and tRNA coding regions, especially in ATP8 within complex V and in loop and variable regions within tRNA, were significantly lower than those in other regions. While the mutation rate of most codons and amino acids were consistent with the expectation under neutrality, several codons and amino acids had significantly different rates. Moreover, the mutations under selection were enriched for changes that are predicted to be deleterious, further supporting the evolutionary constraints on these regions.ConclusionThese results indicate the existence of site-specific selection and imply the important role of the mtDNA mutations at some specific sites in tumor development.Electronic supplementary materialThe online version of this article (10.1186/s13046-017-0638-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations

Guo

et al. 2017

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Furthermore, the incidence rates of head and neck cancer have risen in many countries over the past decade 2 . Although better combinations of loco-regional plus systemic therapeutic modalities have improved the quality of life after treatment, the 5-year survival rate has not changed much in recent years 3 4 .…”

mentioning

confidence: 99%

Microsatellite alteration in head and neck squamous cell carcinoma patients from a betel quid-prevalent region

Lin

Wang

Jiang

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

We investigated the frequency of microsatellite alteration and their impact on survival in head and neck squamous cell carcinoma patients from an endemic betel quid chewing area. We collected 116 head and neck squamous cell carcinoma specimens along with corresponding surgical margins which were confirmed by pathological examination. Ten oligonucleotide markers were chosen for the assessment of microsatellite alteration. The specimens were amplified by polymerase chain reaction followed by automatic fragment analysis. There were 44 specimens (37.9%) with microsatellite instability (MSI) in at least one marker while more than half of the specimens (n = 68, 58.6%) had loss of heterozygosity (LOH) in at least one marker. Though MSI/LOH was not correlated with the survival of head and neck squamous cell carcinoma patients, presence of MSI in the tumor-free surgical margins was associated with local recurrence (odds ratio: 15.14; 95% confidence interval: 6.451 ~ 35.53; P < 0.001). Genomic assessment of surgical margin can help surgeons to identify head and neck squamous cell carcinoma patients who are at risk of developing local recurrence in a betel quid-prevalent region.

show abstract

“…One more interesting observation is that chewers (24 %, i.e., n=14) are more susceptible to mtDNA mutation compared to smokers (10 %, i.e., n=3) ( Table 4). This might be due to oxidative DNA damage inflicted by generation of more ROS in oral cavity of chewers who used tobacco, areca nuts and lime, and same has been observed in other studies [41,42] although recent data suggests that most of the mtDNA mutations in tumor arose during replication of mtDNA [35]. Previously, most of the reports have done crude estimates to compare the incidence of mutations among patients and controls.…”

Section: Discussionmentioning

confidence: 74%

“…Mutations in mtDNA have been reported in different cancers and most of such mutations accumulate in D-loop which is a control region of mitochondria replication and transcription [10,14,22,41,42]. Over the years, several studies have reported mutations in D-loop of different cancers though mutation rates have been highly variable: 21, 29, and 62 % of samples were reported to harbor D-loop mutations in head and neck cancer [9,12,16], 35 % of samples were found to harbor D-loop mutations in gastric cancer [22] whereas in cervical cancer, 95 % of the samples were reported to have mutated D-loop [14].…”

Section: Discussionmentioning

confidence: 99%

D-loop somatic mutations and ∼5 kb “common” deletion in mitochondrial DNA: important molecular markers to distinguish oral precancer and cancer

et al. 2014

View full text Add to dashboard Cite

Apart from genomic DNA, mutations at mitochondrial DNA (mtDNA) have been hypothesized to play vital roles in cancer development. In this study, ∼5 kb deletion and D-loop mutations in mtDNA and alteration in mtDNA content were investigated in buccal smears from 104 healthy controls and 74 leukoplakia and 117 cancer tissue samples using Taqman-based quantitative assay and re-sequencing. The ∼5 kb deletion in mtDNA was significantly less (9.8 and 10.5 folds, P < 0.0001) in cancer tissues compared to control and leukoplakia tissues, respectively. On the other hand, somatic mutations in D-loop, investigated in 54 controls, 50 leukoplakias and 56 cancer patients, were found to be significantly more in cancer tissues, but not in leukoplakia tissues, compared to control (Z-score = 5.4). MtDNA contents were observed to be significantly more in leukoplakia (2.1 folds, P = 0.004) and cancer (1.6 folds, P = 0.03) tissues compared to control tissues. So, D-loop somatic mutations and ∼5 kb deletion patterns could be used as distinguishing markers between precancer and cancer tissues. This observation further suggests that somatic mutations in D-loop may facilitate carcinogenesis and cancer cells with less ∼5 kb deletion, i.e., intact mtDNA, may become resistant to apoptosis.

show abstract

Somatic mutations in the D‐loop of mitochondrial DNA in head and neck squamous cell carcinoma

Abstract: Somatic mutation of D-loop of mtDNA was a potential prognostic factor of head and neck squamous cell carcinoma.

Cited by 11 publications

References 21 publications

Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations

Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations

Microsatellite alteration in head and neck squamous cell carcinoma patients from a betel quid-prevalent region

D-loop somatic mutations and ∼5 kb “common” deletion in mitochondrial DNA: important molecular markers to distinguish oral precancer and cancer

Contact Info

Product

Resources

About