Screening And Analysis Of Mutation In Nijmegen Breakage Syndrome Gene(NBS1) In Primary Liver Cancer

Background and aim:Primary liver cancer(PLC) is a common malignant tumor, which the third of the word tumor spectrum. In our country the incidence of the PLC was28.17/105, the cancer mortality was25.84/105which the third of the tumor mortality spectrum, PLC increase year by year. The incidence and mortality of PLC even leaps to the first in some area. The concrete cause and mechanism of PLC is still unclear, but it generally was considered that many factors, ways, steps participated in this process. The results of the researches showed PLC was associationed with the flaws of DNA damage mechanisms and the inactivation of tumor suppressor gene. NBS1is a DNA damage repair gene. It was mapped to chromosome8q21, consists of16exons. The variability of the sequence is very large. It encodes the Nbsl that DNA double-strand breaks(DSBs) mainly repair protein. The Nbsl protein is a component of the Mrell/Rad50/Nbsl complex, which acts as a sensor of DNA double-strand breaks, functioning in cell cycle checkpoint in response to DNA damage, and is critical for maintaining genomic stability. In the present study, we explored the role of NBS1in primary liver cancer, including HBV-associated hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).Method:NBS1was screened and identified by SSCP (single strand conformation polymorphism) analysis followed by direct sequencing. Genetic alteration in TP53pathway was identified by detection of TP53mutations (the methods was the same as the NBS1), MDM2amplification and p14ARF homozygous deletion (differential PCR), p14ARF promoter methylation(methylation-specific PCR).Results:Miscoding NBS1mutations were identified in7of64(10.9%) HCC and2of18(11.1%) ICC, but not found in89cases of cirrhosis and chronic hepatitis B.8out of9tumors with NBS1mutations contained at least one genetic alteration in the p53pathway, and there was a significantly association between them. Conclusion:The mutations of NBS1in the PLC was higher than the congtrol. NBSl mutations in the PLC was association the inactivation of TP53pathway. These may contribute to the development and progression of primary liver cancer.