Mitochondrial DNA minisatellites as new markers for the quantitative determination of hematopoietic chimerism after allogeneic stem cell transplantation

Mg, Shin; Kim, Hyung Jun; Hr, Kim; Lee, IK; Kook, Hoon; D, Cho; Sj, Kee; Shin, JH; Sp, Suh; Dw, Ryang

doi:10.1038/sj.leu.2404502

Cited by 6 publications

(10 citation statements)

References 8 publications

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“…The three mtDNA minisatellite markers, such as 16189 poly C ( 16184 CCCCCTCCCC 16193 , 5CT4C), 303 poly C ( 303 CCCCCCCTCCCCC 315 , 7CT5C) and 514 (CA) repeat ( 514 CACACACACA 523 , (CA) 5 repeats) in mtDNA noncoding hypervariable regions (HV) 1 and 2 were used for checking mtDNA instability of colon cancer tissue and corresponding adjacent normal mucosa (Supporting Information Table 2). The method of analysis was size‐based separation of amplified product by capillary electrophoresis based on our published protocol 11, 12. Thymine Adenine cloning for the confirmation of mtDNA minisatellite alterations was carried out according to a previously published protocol 11…”

Section: Methodsmentioning

confidence: 99%

High‐frequency minisatellite instability of the mitochondrial genome in colorectal cancer tissue associated with clinicopathological values

Lim

Kim

et al. 2012

Intl Journal of Cancer

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Most studies of mitochondrial DNA (mtDNA) mutations in colorectal cancer have used case-control and case-database comparisons without searching their clinical relevance. This study was to investigate colorectal cancer tissue-specific mtDNA mutations from 54 matched colorectal cancer and adjacent normal tissues and then to evaluate their clinical values. This study focused on analyzing control region including mtDNA minisatellites and coding regions. Cancer tissue-specific mtDNA mutations were found in over half of the patients (59%). The patterns of mtDNA mutations were substitution only (13%), mtDNA minisatellite instability (mtMSI) (20%) and both mutations combined (26%). mtMSI in colorectal cancer was mainly occurred in the 303 polyC (35%) and 16184 poly C (19%) minisatellite. mtDNA copy number and hydrogen peroxide level were significantly increased in colorectal cancer tissue. The amount of mtDNA large deletions was significantly decreased in colorectal cancer tissue compared with those from matched normal mucosa (p 5 0.03). The activity of the mitochondrial respiratory chain enzyme complexes I, II and III in colorectal cancer tissues was impaired. mtDNA haplogroup B4 might be closely associated with colorectal cancer risk. The patient group harboring cancer tissue-specific mtDNA mutations showed larger tumor sizes (p 5 0.005) and more advanced TNM stages (p 5 0.002). Thus, mtDNA mutations in colorectal cancer might be implicated in risk factors that induce poor outcomes and tumorigenesis.

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Section: Methodsmentioning

confidence: 99%

High‐frequency minisatellite instability of the mitochondrial genome in colorectal cancer tissue associated with clinicopathological values

Lim

Kim

et al. 2012

Intl Journal of Cancer

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“…Size-based amplified product separation by capillary electrophoresis based on published protocol was performed in order to detect length heteroplasmic mutations of 16189 poly C ( 16184 CCCCCTCCCC 16193 , 5CT4C), 303 poly C ( 303 CCCCCCCTCCCCC 315 , 7CT5C) and 514 (CA) repeat ( 514 CACACACACA 523 , (CA)5 repeats) [20], [21] (Table S2). …”

Section: Methodsmentioning

confidence: 99%

Frequent Occurrence of Mitochondrial DNA Mutations in Barrett’s Metaplasia without the Presence of Dysplasia

et al. 2012

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BackgroundBarrett's esophagus (BE) is one of the most common premalignant lesions and can progress to esophageal adenocarcinoma (EA). The numerous molecular events may play a role in the neoplastic transformation of Barrett’s mucosa such as the change of DNA ploidy, p53 mutation and alteration of adhesion molecules. However, the molecular mechanism of the progression of BE to EA remains unclear and most studies of mitochondrial DNA (mtDNA) mutations in BE have performed on BE with the presence of dysplasia.Methods/FindingsThus, the current study is to investigate new molecular events (Barrett’s esophageal tissue-specific-mtDNA alterations/instabilities) in mitochondrial genome and causative factors for their alterations using the corresponding adjacent normal mucosal tissue (NT) and tissue (BT) from 34 patients having Barrett’s metaplasia without the presence of dysplasia. Eighteen patients (53%) exhibited mtDNA mutations which were not found in adjacent NT. mtDNA copy number was about 3 times higher in BT than in adjacent NT. The activity of the mitochondrial respiratory chain enzyme complexes in tissues from Barrett’s metaplasia without the presence of dysplasia was impaired. Reactive oxygen species (ROS) level in BT was significantly higher than those in corresponding samples.Conclusion/SignificanceHigh ROS level in BT may contribute to the development of mtDNA mutations, which may play a crucial role in disease progression and tumorigenesis in BE.

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“…The final PBS suspension contained 1 Â 10 7 cells/mL. Total DNA was extracted using the QIAamp Blood Mini Kits (Qiagen, Hilden, Germany) according to the manufacturer's instructions and resuspended in TE buffer (10 mM Tris-HCl and 1 mM EDTA; pH 8.0), then quantified spectrophotometrically [8].…”

Section: Preparation Of Donor and Recipient Samplesmentioning

confidence: 99%

“…We chose 3 mtMS markersd303 poly C, 16184 poly C, and 514 (CA) repeatdbased on our findings in a previous study [8]. We analyzed the informativeness of the mtMS markers compared with nuclear STR markers using clinical records.…”

Section: Chimerism Assay Using Mtms and Nuclear Str Markersmentioning

confidence: 99%

“…Mitochondrial DNA (mtDNA) also has high variability and numerous polymorphisms, which have been used to examine personal identification and phylogenetic relationships. We previously reported that mtDNA minisatellite (mtMS) markers generally have higher sensitivity and accuracy compared with nuclear STR markers [7,8]. These beneficial attributes have been applied only to small and limited sets of hematologic disorders, however, which might not represent sufficient laboratory performance, especially in inappropriately obtained specimens, or accurately reflect the clinical value of mtMS markers in quantitatively determining MC after allo-HSCT.…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic and Prognostic Value of Mitochondrial DNA Minisatellites after Stem Cell Transplantation

Won

Kim

et al. 2013

Biology of Blood and Marrow Transplantation

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Mitochondrial DNA has been used to investigate phylogenetic relationships and pathophysiologic roles in aging, degenerative diseases, and cancer. We investigated the prognostic usefulness of mitochondrial DNA minisatellite (mtMS) markers compared with nuclear short tandem repeat markers by evaluating the laboratory performance and clinical value of these markers in a large sample of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with various simulated conditions in vitro and in serial follow-up samples. We examined the value of mtMS markers as a prognostic indicator in 100 patients with various hematologic disorders undergoing allo-HSCT, including 35 patients with longitudinal follow-up for 55 months. The mtMS markers showed high sensitivity and accuracy for the quantitative detection of chimerism compared with nuclear short tandem repeat markers, particularly in unrelated transplantation and under inappropriate sampling conditions. Longitudinal follow-up after allo-HSCT disclosed that chimerism precisely reflected the status of engraftment or relapse during the clinicopathological course. Moreover, changes in mtMS markers in recipients before allo-HSCT were associated with clinical outcomes. Our data indicate that mtMS markers have multiple functions in monitoring mixed chimerism and predicting prognosis after allo-HSCT.

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Mitochondrial DNA minisatellites as new markers for the quantitative determination of hematopoietic chimerism after allogeneic stem cell transplantation

Cited by 6 publications

References 8 publications

High‐frequency minisatellite instability of the mitochondrial genome in colorectal cancer tissue associated with clinicopathological values

High‐frequency minisatellite instability of the mitochondrial genome in colorectal cancer tissue associated with clinicopathological values

Frequent Occurrence of Mitochondrial DNA Mutations in Barrett’s Metaplasia without the Presence of Dysplasia

Diagnostic and Prognostic Value of Mitochondrial DNA Minisatellites after Stem Cell Transplantation

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