Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis.
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.
Department of Anatomy, Keimyung University School of Medicine, Daegu, Republic of Korea.
Jae-Ho
JH
Lee
Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea.
Ilseon
I
Hwang
Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea.
Yu-Na
YN
Kang
Department of Anatomy, Keimyung University School of Medicine, Daegu, Republic of Korea.
In-Jang
IJ
Choi
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.
Dae-Kwang
DK
Kim
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D004272:DNA, Mitochondrial; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins