AIM:One of the characteristics of hepatocellular carcinoma(HCC)in Qidong area is the selective mutation resulting in aserine substitution at codon 249 of the p53 gene(1,20),and it has been identified as a“hotspot”mutation inheptocellular carcinomas occurring in populations exposedto aflatoxin and with high prevalence of hepatitis B viruscarriers(2,3,9,10,16,24).We evaluated in this paperwhether this“hotspot”mutation could be detected in cell-free DNA circulating in plasma of patients with hepatocellularcarcinoma and cirrhosis in Qidong,China,and tried to illustratethe significance of the detection of this molecular biomarker.METHODS:We collected blood samples from 25hepatocellular carcinoma patients,20 cirrhotic patients and30 healthy controls in Qidong area.DNA was extracted andpurified from 200 μl of plasma from each sample.The 249~(Ser)p53 mutation was detected by restriction digestion analysisand direct sequencing of exon-7 PCR products.RESULTS:We found in exon 7 of p53 gene G→T transversionat the third base of codon 249 resulting 249~(Arg)→249~(Ser)mutation in 10/25(40 %)hepatocellular carcinoma cases,4/20(20 %)cirrhotics,and 2/30(7 %)healthy controls.The adjusted odds ratio for having the mutation was 22.1(95%CI,3.2～91.7)for HCC cases compared to controls.CONCLUSION:These data show that the 249~(Ser)p53mutation in plasma is strongly associated with hepatocellularcarcinoma in Qidong patients.We found this mutation wasalso detected,although it was at a much lower frequency,in plasma DNA of Qidong cirrhotics and healthy controls;We consider that these findings,together with the usualmethod of HCC diagnosis,will give more information in earlydiagnosis of HCC,and 249~(Ser)p53 mutation should bedeveloped to a new early diagnostic marker for HCC. AIM: One of the characteristics of hepatocellular carcinoma (HCC) in Qidong area is the selective mutation resulting in aserine substitution at codon 249 of the p53 gene (1,20), and it has been identified as a “hotspot” mutation inheptocellular carcinomas occurring in populations exposed to aflatoxin and with high prevalence of hepatitis B virus carriers (2,3,9,10,16,24) .We evaluated in this paperwhether this “hotspot ” mutation could be detected in cell-free DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis in Qidong, China, and tried to illustrate the significance of the detection of this molecular biomarker. METHODS: We collected blood samples from 25 patients with epithelial cells, 20 cirrhotic patients and 30 healthy controls in Qidong area. DNA was extracted and purified from 200 μl of plasma from each sample. 249 ~ (Ser) p53 mutation was detected by restriction digestion analysis and direct sequencing of exon-7 PCR products.RESULTS: We found in exon 7 of p53 gene G → T transversionat the third base of codon 249 resulting in 249 ~ (Arg) → 249 ~ (Ser) mutation in 10/25 (40%) hepatocellular carcinoma cases, 4/20 (20%) cirrhotics, and 2/30 ) healthy controls. The adjusted odds ratio for having the mutation was 22.1 (95% CI, 3.2-91.7) for HCC cases compared to controls. CONCLUSION: These data show that the 249 ~ (Ser) p53 mobilization in plasma is strongly associated with hepatocellular carcinoma in Qidong patients. We found this mutation wasalso detected, although it was at a much lower frequency, in plasma DNA of Qidong cirrhotics and healthy controls; We consider that these findings, together with the usualmethod of HCC diagnosis, will give more information in early diagnosis of HCC, and 249 ~ (Ser) p53 mutation should bedeveloped to a new early diagnostic marker for HCC.