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The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer.

Chen T, He J, Shen L, Fang H, Nie H, Jin T, Wei X, Xin Y, Jiang Y, Li H, Chen G, Lu J, Bai Y - BMC Med. Genet. (2011)

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine of Wenzhou Medical College, Zhejiang 325035, PRChina.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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Related in: MedlinePlus

Relationship between mtDNA content and cancer stage. mtDNA content is plotted again the cancer stage in tumor (closed circle) and non-tumor (open circle) tissues of patients (A) with the 4, 977-bp mtDNA deletion, and (B) without the deletion.
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Figure 6: Relationship between mtDNA content and cancer stage. mtDNA content is plotted again the cancer stage in tumor (closed circle) and non-tumor (open circle) tissues of patients (A) with the 4, 977-bp mtDNA deletion, and (B) without the deletion.

Mentions: To further determine if the mtDNA copy number could also serve as a biomarker for development of colorectal cancer, we analyzed the relationship between mtDNA copy number and cancer stage in these patients. Since we showed previously that in patients with the common deletion, cancer stage was correlated with the 4,977-bp deletion level (Table 2), we examined the relationship between mtDNA content and cancer stage in patients with and without the common deletion. As shown in Figure. 6, in patients with the 4,977-bp deletion, it appeared that as the cancer stage advanced, the mtDNA copy number increased (p = 0.056) in the tumors, while no such correlation was observed in the nearby non-tumor areas (p = 0.151) (Figure. 6A). The correlation between mtDNA content in tumor tissues and cancer stage became stronger and significant after multiple linear regression analysis (p < 0.001) (Table 3). However, in the 18 age- and gender-matched patients without the common deletion, no correlations were detected in both tumor and non-tumor tissues (Figure. 6B and Table 3). To further investigate the implication of mtDNA common deletion and mtDNA content in colorectal cancer patients, we carried out a multiple linear regression analysis of relationship between mtDNA content and age, metastasis status and cancer stage in tumor and non-tumor tissues in patients with or without the common deletion. As shown in Table 3, significant correlations only existed in tumor tissues of colorectal cancer patients carrying the mtDNA common deletion. Besides the cancer stage, with increasing mtDNA copy number in tumor tissues with the common deletion, the cancer was more likely to be LN metastatic (p = 0.002).


The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer.

Chen T, He J, Shen L, Fang H, Nie H, Jin T, Wei X, Xin Y, Jiang Y, Li H, Chen G, Lu J, Bai Y - BMC Med. Genet. (2011)

Relationship between mtDNA content and cancer stage. mtDNA content is plotted again the cancer stage in tumor (closed circle) and non-tumor (open circle) tissues of patients (A) with the 4, 977-bp mtDNA deletion, and (B) without the deletion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3025938&req=5

Figure 6: Relationship between mtDNA content and cancer stage. mtDNA content is plotted again the cancer stage in tumor (closed circle) and non-tumor (open circle) tissues of patients (A) with the 4, 977-bp mtDNA deletion, and (B) without the deletion.
Mentions: To further determine if the mtDNA copy number could also serve as a biomarker for development of colorectal cancer, we analyzed the relationship between mtDNA copy number and cancer stage in these patients. Since we showed previously that in patients with the common deletion, cancer stage was correlated with the 4,977-bp deletion level (Table 2), we examined the relationship between mtDNA content and cancer stage in patients with and without the common deletion. As shown in Figure. 6, in patients with the 4,977-bp deletion, it appeared that as the cancer stage advanced, the mtDNA copy number increased (p = 0.056) in the tumors, while no such correlation was observed in the nearby non-tumor areas (p = 0.151) (Figure. 6A). The correlation between mtDNA content in tumor tissues and cancer stage became stronger and significant after multiple linear regression analysis (p < 0.001) (Table 3). However, in the 18 age- and gender-matched patients without the common deletion, no correlations were detected in both tumor and non-tumor tissues (Figure. 6B and Table 3). To further investigate the implication of mtDNA common deletion and mtDNA content in colorectal cancer patients, we carried out a multiple linear regression analysis of relationship between mtDNA content and age, metastasis status and cancer stage in tumor and non-tumor tissues in patients with or without the common deletion. As shown in Table 3, significant correlations only existed in tumor tissues of colorectal cancer patients carrying the mtDNA common deletion. Besides the cancer stage, with increasing mtDNA copy number in tumor tissues with the common deletion, the cancer was more likely to be LN metastatic (p = 0.002).

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine of Wenzhou Medical College, Zhejiang 325035, PRChina.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Show MeSH
Related in: MedlinePlus