Mitochondrial dysfunction has been long proposed to play a major role in tumorigenesis. Mitochondrial DNA (mtDNA) mutations, especially the mtDNA 4,977 bp deletion has been found in patients of various types of cancer. In order to comprehend the mtDNA 4,977 bp deletion status in various cancer types, we performed a meta-analysis composed of 33 publications, in which a total of 1613 cancer cases, 1516 adjacent normals and 638 healthy controls were included. When all studies were pooled, we found that cancerous tissue carried a lower mtDNA 4,977 bp deletion frequency than adjacent non-cancerous tissue (OR = 0.43, 95% CI = 0.20–0.92, P = 0.03 for heterogeneity test, I2 = 91.5%) among various types of cancer. In the stratified analysis by cancer type the deletion frequency was even lower in tumor tissue than in adjacent normal tissue of breast cancer (OR = 0.19, 95% CI = 0.06–0.61, P = 0.005 for heterogeneity test, I2 = 82.7%). Interestingly, this observation became more significant in the stratified studies with larger sample sizes (OR = 0.70, 95% CI = 0.58–0.86, P = 0.0005 for heterogeneity test, I2 = 95.1%). Furthermore, when compared with the normal tissue from the matched healthy controls, increased deletion frequencies were observed in both adjacent non-cancerous tissue (OR = 3.02, 95% CI = 2.13–4.28, P<0.00001 for heterogeneity test, I2 = 53.7%), and cancerous tissue (OR = 1.36, 95% CI = 1.04–1.77, P = 0.02 for heterogeneity test, I2 = 83.5%). This meta-analysis suggests that the mtDNA 4,977 bp deletion is often found in cancerous tissue and thus has the potential to be a biomarker for cancer occurrence in the tissue, but at the same time being selected against in various types of carcinoma tissues. Larger and better-designed studies are still warranted to confirm these findings.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral carcinoma. Mitochondrial DNA (mtDNA) is a circular DNA molecule of 16,569 bp, which functionally encompasses a regulatory non-coding region (D-loop) and 37 encoding genes that correspond to 13 subunits of respiratory chain complexes (I, III, IV and V), 22 transfer RNAs and 2 ribosomal (r)RNAs. Recently, mtDNA has been implicated as a mutation hotspot in various tumors. However, to our knowledge mtDNA alteration in TSCC has not been investigated to date. In the present study, the mitochondrial genomes of tongue carcinoma, adjacent non-cancerous tissue and peripheral blood samples from 8 patients with TSCC were sequenced and aligned with the revised Cambridge Reference Sequence. Overall, only one synonymous mutation, which mapped to the NADH:ubiquinone oxidoreductase core subunit 5 gene, was observed in the tongue carcinoma sample from a single patient. A further 21 polymorphisms were identified, including six in the non-coding region (D-loop), five in Complex I, three in Complex III, two in Complex Ⅳ, two in Complex V and three in rRNA. In addition, mitochondrial microsatellite instability (mtMSI) was detected in 2/8 tongue carcinoma samples, and localized in the D310 region. These variations, particularly the polymorphisms and mtMSI, imply that the mitochondrial genome may be a hotspot of genome alteration in tongue cancer. Further investigation is expected to reveal the role of mtDNA alteration in TSCC development, as well as its clinical implications.

Mitochondrial DNA (mtDNA) mutations played crucial roles on affecting the susceptibility to cancer. In this study, to investigate whether mitochondrial DNA mutations contributed to the genetic susceptibility of Chinese tongue cancer patients, mtDNA control regions of 105 Chinese tongue cancer patients were amplified and sequenced, the mutations were recorded by comparing with the revised Cambridge Reference Sequence (rCRS), which were attributed to certain mtDNA haplogroups based on the specific variations motif of each patients. The Miao Chinese group (a Chinese ethnic minority) from surrounding region has no essential difference with tongue cancer group, which was taken as the matched control group with principal component analysis by taking the haplogroups frequency of 105 tongue cancer individuals and 354 healthy individuals of eight groups from the similar geographic regions as input factors. This was supported by the smallest genetic distance between tongue cancer and Miao_2 groups. Further, the statistical analysis based on mtDNA variations of hypervariable sequence I (HVSI) indicated that 13 variations including 16,124, 16,148, 16,182C, 16,183C, 16,227, 16,266A, 16,249, 16,272, 16,291, 16,327, 16,335, 16,497, and 16,519 have significant differences between tongue cancer group and matched control group. Comparison of mtDNA haplogroups between tongue cancer and control groups indicated that mtDNA haplogroups C, F2*, and M10 have significant differences. It's worth noting that 16,327 and 16,291 was the defining variation of haplogroups C and F2*, respectively. Our results suggested that mitochondrial DNA may play a crucial role for the maternal genetic susceptibility of tongue cancer patients from Hunan, central of China.

Key Clinical MessageWe report two heterozygous carriers of c.464A>G variation in the GJB2 gene in a Chinese pedigree. The proband with hearing loss most likely inherited the c.464A>G variation from his mother who also carries heterozygous c.79G>A variation and has normal hearing. The pathological significance of c.464A>G variation remains to be determined.