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Mitochondrial DNA polymorphisms, its copy number change and outcome in colorectal cancer.

Mohideen AM, Dicks E, Parfrey P, Green R, Savas S - BMC Res Notes (2015)

Bottom Line: Associations of these mtDNA variations with OS and DFS were tested using the Cox regression method.In both univariate and multivariable analyses, none of the six mtDNA polymorphisms were associated with OS or DFS. 39.6 and 60.4% of the patients had increased and decreased mtDNA copy number in their tumor tissues when compared to their non-tumor rectum or colon tissues, respectively.However, in contrast to previous findings, the change in the mtDNA copy number was associated with neither OS nor DFS in our patient cohort.

View Article: PubMed Central - PubMed

Affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, HSC, Room H4333, St. John's, NL, A1B 3V6, Canada. amhm38@med.mun.ca.

ABSTRACT

Background: Mitochondrion is a small organelle inside the eukaryotic cells. It has its own genome (mtDNA) and encodes for proteins that are critical for energy production and cellular metabolism. Mitochondrial dysfunctions have been implicated in cancer progression and may be related to poor prognosis in cancer patients. In this study we hypothesized that genetic variations in mtDNA are associated with clinical outcome in colorectal cancer patients.

Methods: We tested the associations of six mtDNA polymorphisms [MitoT479C, MitoT491C, MitoT10035C, MitoA13781G, 10398 (A/G), and 16189 (T/C)] and the mtDNA copy number change with overall survival (OS) and disease-free survival (DFS) times. Two mtDNA polymorphisms were genotyped using the TaqMan(®) SNP genotyping technique and the genotypes for the remaining four mtDNA polymorphisms were obtained by the Illumina(®) HumanOmni1-Quad genome wide SNP genotyping platform in 536 patients. The mtDNA copy number change (in tumor tissues with respect to non-tumor tissues) was estimated using the quantitative real time polymerase chain reaction for 274 patients. Associations of these mtDNA variations with OS and DFS were tested using the Cox regression method.

Results: In both univariate and multivariable analyses, none of the six mtDNA polymorphisms were associated with OS or DFS. 39.6 and 60.4% of the patients had increased and decreased mtDNA copy number in their tumor tissues when compared to their non-tumor rectum or colon tissues, respectively. However, in contrast to previous findings, the change in the mtDNA copy number was associated with neither OS nor DFS in our patient cohort.

Conclusions: Our results suggest that the mitochondrial genetic markers investigated in this study are not associated with outcome in colorectal cancer.

No MeSH data available.


Related in: MedlinePlus

The mtDNA ratio in tumor tissue versus non-tumor tissues in the patients.
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Fig1: The mtDNA ratio in tumor tissue versus non-tumor tissues in the patients.

Mentions: Results of the mtDNA copy number analysis obtained in 274 of 276 colorectal cancer patients are summarized in Figure 1. In this patient cohort, the ratio of mtDNA in tumor to non-tumor tissue (mtDNAT/N) varied between 0.003 and 11. The majority (94.8%) of the mtDNAT/N were less than 3. In rare cases, a considerable increase in tumor mtDNA was observed (patients with mtDNAT/N ratios ≥3–11, n = 14). An inspection of the clinicopathological features of these 14 patients showed a tendency towards having tumors with stage III and IV (10 out of 14), with MSS/MSI-L (13 out of 14) and with no BRAF1-Val600Glu mutation (13 out of 14; the remaining patient’s BRAF1 mutation status was not determined).Figure 1


Mitochondrial DNA polymorphisms, its copy number change and outcome in colorectal cancer.

Mohideen AM, Dicks E, Parfrey P, Green R, Savas S - BMC Res Notes (2015)

The mtDNA ratio in tumor tissue versus non-tumor tissues in the patients.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482280&req=5

Fig1: The mtDNA ratio in tumor tissue versus non-tumor tissues in the patients.
Mentions: Results of the mtDNA copy number analysis obtained in 274 of 276 colorectal cancer patients are summarized in Figure 1. In this patient cohort, the ratio of mtDNA in tumor to non-tumor tissue (mtDNAT/N) varied between 0.003 and 11. The majority (94.8%) of the mtDNAT/N were less than 3. In rare cases, a considerable increase in tumor mtDNA was observed (patients with mtDNAT/N ratios ≥3–11, n = 14). An inspection of the clinicopathological features of these 14 patients showed a tendency towards having tumors with stage III and IV (10 out of 14), with MSS/MSI-L (13 out of 14) and with no BRAF1-Val600Glu mutation (13 out of 14; the remaining patient’s BRAF1 mutation status was not determined).Figure 1

Bottom Line: Associations of these mtDNA variations with OS and DFS were tested using the Cox regression method.In both univariate and multivariable analyses, none of the six mtDNA polymorphisms were associated with OS or DFS. 39.6 and 60.4% of the patients had increased and decreased mtDNA copy number in their tumor tissues when compared to their non-tumor rectum or colon tissues, respectively.However, in contrast to previous findings, the change in the mtDNA copy number was associated with neither OS nor DFS in our patient cohort.

View Article: PubMed Central - PubMed

Affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, HSC, Room H4333, St. John's, NL, A1B 3V6, Canada. amhm38@med.mun.ca.

ABSTRACT

Background: Mitochondrion is a small organelle inside the eukaryotic cells. It has its own genome (mtDNA) and encodes for proteins that are critical for energy production and cellular metabolism. Mitochondrial dysfunctions have been implicated in cancer progression and may be related to poor prognosis in cancer patients. In this study we hypothesized that genetic variations in mtDNA are associated with clinical outcome in colorectal cancer patients.

Methods: We tested the associations of six mtDNA polymorphisms [MitoT479C, MitoT491C, MitoT10035C, MitoA13781G, 10398 (A/G), and 16189 (T/C)] and the mtDNA copy number change with overall survival (OS) and disease-free survival (DFS) times. Two mtDNA polymorphisms were genotyped using the TaqMan(®) SNP genotyping technique and the genotypes for the remaining four mtDNA polymorphisms were obtained by the Illumina(®) HumanOmni1-Quad genome wide SNP genotyping platform in 536 patients. The mtDNA copy number change (in tumor tissues with respect to non-tumor tissues) was estimated using the quantitative real time polymerase chain reaction for 274 patients. Associations of these mtDNA variations with OS and DFS were tested using the Cox regression method.

Results: In both univariate and multivariable analyses, none of the six mtDNA polymorphisms were associated with OS or DFS. 39.6 and 60.4% of the patients had increased and decreased mtDNA copy number in their tumor tissues when compared to their non-tumor rectum or colon tissues, respectively. However, in contrast to previous findings, the change in the mtDNA copy number was associated with neither OS nor DFS in our patient cohort.

Conclusions: Our results suggest that the mitochondrial genetic markers investigated in this study are not associated with outcome in colorectal cancer.

No MeSH data available.


Related in: MedlinePlus