ObjectiveTo determine the frequency and type of p16 gene homozygous deletion and mutation with the progression of human gastric carcinogenesis.MethodsPCR （polymerase chain reaction），SSCP (single strand conformation polymorphism) and DNA sequencing were performed on 50 operative tissues, which included 7 early gastric cancer and 43 advanced gastric cancer. In this group there were 36 male and 14 female patients aged 35 to 68,which included 30 welldifferetiated adenocarcinoma and 20 poordifferentiated carcinoma; 19 patients with lymph node metastases.ResultsTotal mutation frequency of p16 gene was 8.00%(4/50), including 14.29%(1/7) of early cancer and 7.00%(3/43) of advanced cancer，there was no significant difference between early and advanced cancer （P＞0.05）. In addition, p16 gene mutation was not related to site，location，grade of tumor differentiation and lymph node metastases, respectively. Total deletion frequency of p16 gene was 16.00%(8/50), of which 18.60%(8/43) was detected in advanced cancer, but no cases in early cancers. There was a significant difference between early and advanced cancer （P＜0.05）, and frequency p16 gene homozygous deletion was related to grade of tumor differentiation and lymph node metastases, respectively. Direct DNA sequencing displayed that 4 point mutations detected in 99,125,433,441 base, there were 3 missense mutation and 1 samesense mutation, no deletion or insertion was found. Conclusionp16 gene mutation is an early event in gastric carcinogenesis，it helps early diagnosis of human gastric carcinoma. p16 gene homozygous deletion is a late event in gastric carcinogenesis，it might relate to metastases and recurrence of gastric cancer.
Citation：
SUN Haijun,WU Bo,LI Aidong,et al. Deletion and Mutation of p16/mts1 Gene in Human Gastric Cancer of Different Periods. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2002, 9(6): 415-417. doi:
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- 1. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985 [J]. Int J Cancer,1993； 54（4）∶594.
- 2. Wright PA,Williams GT. Molecular biology and gastric carcinoma [J]. Gut,1993； 34（2）∶145.
- 3. 刘君，李宁，蒲永东，等. 抑癌基因p16在人胃癌中的表达及其临床意义 [J]. 中国普外基础与临床杂志，1998； 5(5)∶285.
- 4. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning [M]. 2nd ed. New York: Cold Spring Harbor Laboratory Press,1989∶327-328.
- 5. Wu MS，Shun CT, Sheu JC， et al. Overexpression of mutation p53 and cerbB2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma： with respect to histological subtypes and stages [J]. J Gastroenterol Hepatol，1998； 13（3）∶305.
- 6. Gunther T，SchneiderStock R, Pross M, et al. Alterations of the p16/MTS1tumor suppressor gene in gastric cancer [J]. Pathol Res pract， 1998； 194（12）∶809.
- 7. Sakata K，Tamura G，Maesawa C, et al. Loss of heterozygosity on the short arm of chromosome 9 without p16 gene mutation in gastric carcinomas [J]. Jpn J cancer Res，1995; 86(4)∶333.
- 8. Lee YY, Kang SH, Seo JY,et al. Alterations of p16 INK4A and p15 INK4B genes in gastric carcinomas [J]. Cancer， 1997; 80(10)∶1889.
- 9. 刘君综述，蒲永东，宋少柏审校. 胃癌中p16基因研究概况 [J]. 中国普外基础与临床杂志，1999； 6(3)∶190.
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