[Show abstract][Hide abstract] ABSTRACT: The 4977bp common deletion is one of the most frequently observed mitochondrial DNA (mtDNA) mutations in human tissues and has been implicated in various human cancer types. It is generally believed that continuous generation of intracellular reactive oxygen species (ROS) during oxidative phosphorylation (OXPHOS) is a major underlying mechanism for generation of such mtDNA deletions while antioxidant systems, including Manganese superoxide dismutase (MnSOD), mitigating the deleterious effects of ROS. However, the clinical significance of this common deletion remains to be explored. A comprehensive investigation on occurrence and accumulation of the common deletion and mtDNA copy number was carried out in breast carcinoma (BC) patients, benign breast disease (BBD) patients and age-matched healthy donors in our study. Meanwhile, the representative oxidative (ROS production, mtDNA and lipid oxidative damage) and anti-oxidative features (MnSOD expression level and variation) in blood samples from these groups were also analyzed. We found that the mtDNA common deletion is much more likely to be detected in BC patients at relatively high levels while the mtDNA content is lower. This alteration has been associated with a higher MnSOD level and higher oxidative damages in both BC and BBD patients. Our results indicate that the mtDNA common deletion in blood may serve a biomarker for the breast cancer.
[Show abstract][Hide abstract] ABSTRACT: Steroidogenic acute regulatory (StAR) protein is a rate-limiting protein, which is essential for transporting cholesterol into the mitochondria for steroidogenesis. StAR protein could be a marker for steroidogenic tissues. In this study, we investigated StAR protein levels in sex-cord stromal tumors (SCSTs) including 31 adult granulosa cell tumors, 3 juvenile granulosa cell tumors, 10 fibrothecomas, 2 luteinized thecomas, 4 Sertoli-Leydig cell tumors (SLCTs), 4 sclerosing stromal tumor and 3 Leydig cell tumors (LCTs), and 219 non-SCSTs. SCSTs were used for immunohistochemical staining of StAR protein, α-inhibin, calretinin, and CD99. All the 3 LCTs (100%) strongly stained for StAR protein; 30 of the 31 adult granulosa cell tumors (96%) showed focal staining of StAR protein; all the 10 fibrothecomas and 4 sclerosing stromal tumors (100%) were negative for StAR protein staining; StAR protein stained in Leydig cells but not in Sertoli cells in the 4 SLCTs. All the non-SCSTs were negative for StAR protein except for tumor cells in 4 adrenocortical adenomas and 2 adrenocortical carcinomas. Results of the study indicate that StAR protein is a useful marker for differential diagnosis of SCSTs. It is sensitive and specific for Leydig cells in tumors containing this component (LCT, SLCT), and can express focally in granulosa cell tumors. It is negative for Sertoli cells and nonluteinized theca cells.
No preview · Article · May 2011 · Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry
[Show abstract][Hide abstract] ABSTRACT: To evaluate the role of mtDNA in breast cancer.
We carried out an investigation into the mtDNA major control region or D-loop region and an essential and the largest mtDNA protein-coding gene, NADH dehydrogenase subunit 5 (ND5), together with a mitochondrial haplogroup analysis in 64 patients with breast cancer (BC) and 54 patients with benign breast disease (BBD) as controls.
Mutations in D-loop region were found in 10/64 or 15.6% of patients with BC and 14/54 or 25.9% of patients with BBD, while mutations in ND5 were detected in 6/64 or 9.4% of patients with BC and 5/54 or 9.3% of patients with BBD. In addition, in patients with BBD, mtDNA mutations were more likely to rise in D-loop region and the mutations were more likely to be heteroplasmic. However, in patients with BC, those with metastatic feature were less likely to carry mutations in D-loop region. Finally, we found haplogroup M has an increased risk of breast cancer compared with haplogroup N.
mtDNA mutation may play a role in early stage of tumorigenesis, and mitochondrial haplogroup can also modulate breast cancer occurrence.
Full-text · Article · Apr 2011 · Journal of Cancer Research and Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: qualitative and quantitative changes in human mitochondrial DNA (mtDNA) have been implicated in various cancer types. A 4,977 bp deletion in the major arch of the mitochondrial genome is one of the most common mutations associated with a variety of human diseases and aging.
we conducted a comprehensive study on clinical features and mtDNA of 104 colorectal cancer patients in the Wenzhou area of China. In particular, using a quantitative real time PCR method, we analyzed the 4,977 bp deletion and mtDNA content in tumor tissues and paired non-tumor areas from these patients.
we found that the 4,977 bp deletion was more likely to be present in patients of younger age (≤65 years, p = 0.027). In patients with the 4,977 bp deletion, the deletion level decreased as the cancer stage advanced (p = 0.031). Moreover, mtDNA copy number in tumor tissues of patients with this deletion increased, both compared with that in adjacent non-tumor tissues and with in tumors of patients without the deletion. Such mtDNA content increase correlated with the levels of the 4,977 bp deletion and with cancer stage (p < 0.001).
our study indicates that the mtDNA 4,977 bp deletion may play a role in the early stage of colorectal cancer, and it is also implicated in alteration of mtDNA content in cancer cells.
Full-text · Article · Jan 2011 · BMC Medical Genetics
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial DNA (mtDNA) haplogroups and single nucleotide polymorphisms (mtSNP) have been shown to play a role in various human conditions including aging and some neurodegenerative diseases, metabolic diseases and cancer.
To investigate whether mtDNA haplogroups contribute to the occurrence of cancer in a specific Chinese population, we have carried out a comprehensive case-control study of mtDNA from large cohorts of patients with three common cancer types, namely, colorectal cancer (n = 108), thyroid cancer (n = 100) and breast cancer (n = 104), in Wenzhou, a southern Chinese city in the Zhejiang Province.
We found that patients with mtDNA haplogroup M exhibited an increased risk of breast cancer occurrence [OR = 1.77; 95% CI (1.03-3.07); P = 0.040], and that this risk was even more pronounced in a sub-haplogroup of M, D5 [OR = 3.11; 95%CI (1.07-9.06); p = 0.030]. In spite of this, in patients with breast cancer, haplogroup M was decreased in the metastatic group. On the other hand, our results also showed that haplogroup D4a was associated with an increased risk of thyroid cancer [OR = 3.00; 95%CI (1.09-8.29); p = 0.028]. However, no significant correlation has been detected between any mtDNA haplogroups and colorectal cancer occurrence.
Our investigation indicates that mitochondrial haplogroups could have a tissue-specific, population-specific and stage-specific role in modulating cancer development.
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial defects have been associated with various human conditions including cancers.
We analyzed the mutations at the mitochondrial DNA (mtDNA) in patients with different thyroid lesions. In particular, in order to investigate if the accumulation of mtDNA mutations play a role in tumor progression, we studied the highly variable main control region of mtDNA, the displacement-loop (D-loop) in patients with non-tumor nodular goiters, with benign thyroid adenomas, and with malignant thyroid carcinomas. Total thyroid tumor or goiter samples were obtained from 101 patients, matched with nearby normal tissue and blood from the same subject.
Noticeably, mitochondrial microsatellite instability (mtMSI) was detected in 2 of 19 nodular goiters (10.53%), and 8 of 77 (10.39%) malignant thyroid carcinomas. In addition, 6 patients, including 5 (6.49%) with malignant thyroid carcinomas and 1 (5.26%) with nodular goiter, were found to harbor point mutations. The majority of the mutations detected were heteroplasmic.
Our results indicate that mtDNA alterations in the D-loop region could happen before tumorigenesis in thyroid, and they might also accumulate during tumorigenesis.
Full-text · Article · Jun 2009 · Biochimica et Biophysica Acta