The Study On The Instability Of Mitochondrial DNA Microsatellite In Esophageal Cancer

There are various factors and genes leading to the occurrence of tumors which involved the activating the oncogenes,deactivating of anti-oncogenes and the apotosis related genes. At present,it is known that the genetic instability plays an part 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 nMSI and mtMSI. The recent investigations have showed that mtMSI also plays an important part 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. 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 esophageal cancer is mainly involved in tumor suppressor pathway,but a little in microsatellite instability pathway in which no profound research has been carried out at present. Purpose: To explore the role of mtMSI in the developmemt of primary esophageal cancer,and the relationship between mtMSI and nMSI,so as to futher clarify the molecular mechanism in the occurrence of esophageal cancer,and find new methods for clinical diagnosis,therapy and prevention. Materials and methods: Forty-five specimens of the esophageal cancer , adjacent to esophageal cancer lesion and normal tissue were obtained from patients who have been performed operations for primary esophageal cancer in Southwest Hospital in 2002.The methods of PCR-SCCP was used to detect mtMSI and nMSI in esophageal cancer. Two mitochondrial microsatellite sequences within D-loop region and four within coding region were examined to detect mtMSI,while locus BAT26 and D2S123 were examined to detect nMSI.Results: (1) In the forty-five esophageal cancer used for mtMSI detection, at least the mtMSI was detected in 9(20.0%) at a locus,including 8(16.67%) tumor specimens at D-loop region,in 7 at repeated sequence (C)n and 1 at repeated sequence (CA)n within D-loop region.Within coding region,mtMSI was detected in 4 specimens,3 of which at locus ND1 and 1 of which at locus ND5 respectively,none at locus COI\COIII.(2)There was a positive correlation between D-loop region and coding region of mt (P<0.05). (3) The MSI was detected in 9 specimens (20.0%) at locus D2S123,in 3 (6.67%) at locus BAT26. Altogether 10(22.2%) exhibited nMSI was detected at least at a locus. (4)The positive correlation was found between esophageal caner mtMSI and nMSI.(5)Forty-five specimens were divided into groups according to clilicopathological classification,clinical stages,the metastasis of the Lympha node and serosal invasion. No correlation was found between mtMSI/ nMSI and clinical pathological parameters of esophageal caner (P>0.05). Conclusions: (1) The mtMSI may play an important role in some of the esophageal cancer. (2).D-loop region was an important target of mtMSI in esophageal cancer,especially in (C)n repeated sequence. (3) No correlation was found between mtMSI and clinical pathological parameters of esophageal cancer,her early molecular pathway may be involved in it. (4) The positive correlation was found between mtMSI and nMSI in esophageal cancer.