| Genetic instability plays an important role in the occurrence of tumors. This genetic instability includes two different styles: one is chromosomal instability, in another word, tumor suppressor pathway; the other is microsatellite instability (MSI) pathway. MSI includes nuclear MSI and mitochondrial MSI. Investigations have showed that mitochondrial MSI also plays an important role in the occurrence and development of tumors. Independent of nuclear DNA, mitochondrial DNA (mtDNA) possesses active ability of self-replication. Mitochondria contains its own genetic systems for replication, transcription and translation. Mitochondrial DNA in eukaryotic cells is a 16596-base pair (bp) double-stranded, closed circular molecule. In comparison with nuclear genome, mitochondrial DNA is an important target of carcinogens for its small molecular weight, absence of protection by histone, easily attacked by carcinogens and absence of damage repair systems. On the other hand, a high concentration of oxygen in mitochondria produces free radical, hydroperoxide, and so on. While mitochondria can't clean these peroxides by synthesis of glutathione, so oxidation damages may easily occur in mitochondria and mitochondrial DNA . The occurrence of hepatocellular carcinoma (HCC) is mainly involved in tumor suppressor pathway, but not in microsatellite instability pathway in which no profound research has been carried out in the world. Purpose: To explore the role of mitochondrial DNA microsatellite instability (mtMSI) in the developmemt of primary hepatocellular carcinoma,and the relationship between mtMSI and nuclear DNA microsatellite instability (nMSI) to clarify the molecular mechanism in the occurrence of hepatocellular carcinoma, and to find new methods for clinical diagnosis, therapy and prevention.Materials and methods: Fifty-two hepatocellular carcinoma specimens were obtained from patients who have performed operations for primary hepatocellular carcinoma in Southwest Hospital from year 1992 to 1998. Corresponding specimens were obtained from normal liver tissue located para-tumor. The methods of PCR amplification, electrophoresis through polyacrylamide gel and silver staining were used to detect mtMSI and nMSI in hepatocellular carcinoma. Two mitochondrial microsatellite sequences within D-loop region and five within coding region were examined to detect mtMSI, while locus BAT26 was examined to detect nMSI.Results: (1) Fifty-two hepatocellular carcinomas were used for mtMSI detection. The mtMSI was detected in 8 (15.38%) tumor specimens at repeated sequence (C)n within D-loop region, in 2 (3.85%) at repeated sequence (CA)n within D-loop region. Within coding region, mtMSI was detected in 2 (3.85%) specimens at locus ND1, in 1 (1.92%) at locus ND2, none at locus COIII, and mtMSI was detected in 2 (3.85%) specimens at repeated sequence (C)6 and(A)8 of locus ND5, none at repeated sequence (CCT)3 and(AGC)3 of locus ND5. (2) 11 specimens were mtMSI positive in at least one microsatellite locus (21.15%), among them 7 were detected at only one locus (13.46%), 4 were detected at two loci (7.69%) and none at more than 3 loci. Within D-loop region, mtMSI was detected in 10 specimens (19.23%), including 8 specimens at repeated sequence (C)n (80 % of D-loop region), 2 specimens at repeated sequence (CA)n (20% of D-loop region). The mtMSI was detected in 5 specimens (9.62%) within coding region , 4 of which also exhibited mtMSI in D-loop region (80% of coding region). (3)Fifty-two specimens were dividedinto groups according to patients' sex, age, HBsAg positive or negative, with cirrhosis or not, AFP positive or negative. No correlation was found between mtMSI and clinical pathological parameters of HCC (P>0.05). (4) The nMSI was detected in 4 specimens (7.69%) at locus BAT26, one of which also exhibited mtMSI, while 10 exhibited mtMSI among 48 specimens of nMSI negative. Conclusions: (1) The mtMSI occurs not only in gastrointestinal tract tumors, but also in primary hepatocellular carcinoma. It may play an... |
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