Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis

Jae-Ho Lee; Ilseon Hwang; Yu-Na Kang; In-Jang Choi; Dae-Kwang Kim

doi:10.1371/journal.pone.0118612

Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis

PLoS One. 2015 Mar 3;10(3):e0118612. doi: 10.1371/journal.pone.0118612. eCollection 2015.

Authors

Jae-Ho Lee¹, Ilseon Hwang², Yu-Na Kang², In-Jang Choi¹, Dae-Kwang Kim³

Affiliations

¹ Department of Anatomy, Keimyung University School of Medicine, Daegu, Republic of Korea.
² Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea.
³ Department of Medical Genetics, Keimyung University School of Medicine, Daegu, Republic of Korea; Hanvit Institute for Medical Genetics, City Women's Clinic, Buk-gu, Daegu, Republic of Korea.

Abstract

Clinical value of mitochondrial DNA has been described in colorectal cancer (CRC). To clarify its role in colorectal carcinogenesis, mitochondrial microsatellite instability (mtMSI) and other markers were investigated in CRCs and their precancerous lesions, as a multitier genetic study. DNA was isolated from paired normal and tumoral tissues in 78 tubular adenomas (TAs), 34 serrated polyps (SPs), and 100 CRCs. mtMSI, nucleus microsatellite instability (nMSI), KRAS mutation, and BRAF mutation were investigated in these tumors and their statistical analysis was performed. mtMSI was found in 30% of CRCs and 21.4% of precancerous lesions. Mitochondrial copy number was higher in SPs than TAs and it was associated with mtMSI in low grade TAs. KRAS and BRAF mutations were mutually exclusive in TAs and SPs. CRCs with mtMSI showed shorter overall survival times than the patients without mtMSI. In CRCs without nMSI or BRAF mutation, mtMSI was a more accurate marker for predicting prognosis. The genetic change of mitochondrial DNA is an early and independent event in colorectal precancerous lesions and mtMSI and mitochondrial contents are associated with the tubular adenoma-carcinoma sequence, resulting in poor prognosis. This result suggested that the genetic change in mitochondrial DNA appears to be a possible prognosis marker in CRC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics*
Adenocarcinoma / metabolism
Adenocarcinoma / mortality
Adenocarcinoma / pathology
Adenoma / genetics*
Adenoma / metabolism
Adenoma / mortality
Adenoma / pathology
Colonic Polyps / genetics*
Colonic Polyps / metabolism
Colonic Polyps / mortality
Colonic Polyps / pathology
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / mortality
Colorectal Neoplasms / pathology
DNA, Mitochondrial / genetics*
Female
Gene Expression
Humans
Male
Microsatellite Instability
Microsatellite Repeats
Mitochondria / genetics
Mitochondria / pathology
Mutation*
Neoplasm Staging
Prognosis
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins B-raf / metabolism
Proto-Oncogene Proteins p21(ras)
Survival Analysis
ras Proteins / genetics
ras Proteins / metabolism

Substances

DNA, Mitochondrial
KRAS protein, human
Proto-Oncogene Proteins
BRAF protein, human
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)
ras Proteins

Grants and funding

This study was supported by the research promoting grant from the Keimyung University Medical Research Promoting Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.