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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

Comparison of mtDNA content between tumor and non-tumor tissues. mtDNA content in tumor (closed circle) and non-tumor (open circle) tissues are compared in patients (A) carrying the mtDNA 4,977-bp deletion in both tissues (B) carrying the mtDNA 4,977-bp deletion only in tumor tissues, (C) carrying the mtDNA 4,977-bp deletion only in non-tumor tissues, and (D) age and gender matched patients without the deletion. All p values were derived from paired-samples T test analysis.
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Figure 4: Comparison of mtDNA content between tumor and non-tumor tissues. mtDNA content in tumor (closed circle) and non-tumor (open circle) tissues are compared in patients (A) carrying the mtDNA 4,977-bp deletion in both tissues (B) carrying the mtDNA 4,977-bp deletion only in tumor tissues, (C) carrying the mtDNA 4,977-bp deletion only in non-tumor tissues, and (D) age and gender matched patients without the deletion. All p values were derived from paired-samples T test analysis.

Mentions: To verify the difference in mtDNA copy number changes in tumors and nearby non-tumor tissues, we compared them in patients carrying the 4,977-bp deletion in both tumor and non-tumor areas (Figure. 4A), and in patients carrying this deletion only in tumor tissues (Figure. 4B) or only in non-tumor tissues (Figure. 4C). In almost all cases, we found that mtDNA copy numbers were higher in tumor tissues compared with the nearby non tumor areas. To further determine if the 4,977-bp deletion was implicated in the alteration of mtDNA content in colorectal cancer, we also analyzed the mtDNA copy numbers in 18 age- and gender-matched control colorectal cancer patients who did not carry the 4,977-bp deletion. As shown in Figure. 4D, unlike what we observed in patients with the deletion, we did not see a consistent difference in mtDNA copy numbers between tumor and non tumor tissues.


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)

Comparison of mtDNA content between tumor and non-tumor tissues. mtDNA content in tumor (closed circle) and non-tumor (open circle) tissues are compared in patients (A) carrying the mtDNA 4,977-bp deletion in both tissues (B) carrying the mtDNA 4,977-bp deletion only in tumor tissues, (C) carrying the mtDNA 4,977-bp deletion only in non-tumor tissues, and (D) age and gender matched patients without the deletion. All p values were derived from paired-samples T test analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Comparison of mtDNA content between tumor and non-tumor tissues. mtDNA content in tumor (closed circle) and non-tumor (open circle) tissues are compared in patients (A) carrying the mtDNA 4,977-bp deletion in both tissues (B) carrying the mtDNA 4,977-bp deletion only in tumor tissues, (C) carrying the mtDNA 4,977-bp deletion only in non-tumor tissues, and (D) age and gender matched patients without the deletion. All p values were derived from paired-samples T test analysis.
Mentions: To verify the difference in mtDNA copy number changes in tumors and nearby non-tumor tissues, we compared them in patients carrying the 4,977-bp deletion in both tumor and non-tumor areas (Figure. 4A), and in patients carrying this deletion only in tumor tissues (Figure. 4B) or only in non-tumor tissues (Figure. 4C). In almost all cases, we found that mtDNA copy numbers were higher in tumor tissues compared with the nearby non tumor areas. To further determine if the 4,977-bp deletion was implicated in the alteration of mtDNA content in colorectal cancer, we also analyzed the mtDNA copy numbers in 18 age- and gender-matched control colorectal cancer patients who did not carry the 4,977-bp deletion. As shown in Figure. 4D, unlike what we observed in patients with the deletion, we did not see a consistent difference in mtDNA copy numbers between tumor and non tumor tissues.

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