Summary
A nonisotopic screening method based on single-strand DNA conformation analysis (SSCA) was established for the identification of p53 gene alterations in archived tissue samples. The sensitivity of this approach was validated by testing mutations previously identified by direct sequencing. Applying this assay, 40 samples of formalin-fixed, paraffin-embedded tumors, including 33 gastrointestinal carcinoids and seven endocrine pancreatic tumors, were screened. Only one mutation (codon 283, CGC to CCC) was identified in a single clinically benign rectal carcinoid. This mutation occurred during the development of the tumor and was accompanied by loss of the wild-type gene. Our data indicate, that, in contrast to gastrointestinal carcinomas, alterations of the p53 gene are infrequent events in the development of gastrointestinal and pancreatic carcinoids. In addition, there was no evidence for the involvement of p53 in the malignant metastatic progression of carcinoids.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Caron de Fromentel C, Soussi T (1992) TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosom Cancer 4:1–15
Chejfec G, Falkmer S, Askensten U, Grimelius L, Gould VE (1988) Neuroendocrine tumors of the gastrointestinal tract. Pathol Res Pract 183:143–154
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767
Federspiel BH, Burke AP, Sobin LH, Shekita KM (1990) Rectal and colonic carcinoids: A clinicophathologic study of 84 cases. Cancer 65:135–140
Höfler H, Denk H (1984) Immunocytochemical demonstration of cytokeratin in gastrointestinal carcinoids and their probable precursor cells. Virchows Archiv A Pathol Anat 403:235–240
Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB (1992) Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 89:7491–7495
Lohmann D, Horsthemke B, Gillessen-Kaesbach G, Stefani FH, Höfler H (1992) Detection of small RB1 gene deletions in retinoblastoma by multiplex PCR and high-resolution gel electrophoresis. Hum Genet 89:49–53
Lohmann D, Pütz B, Reich U, Böhm J, Präuer H, Höfler H (1993a) Mutational spectrum of the p53 gene in human small-cell lung cancer and relationship to clinico-pathological data. Am J Pathol 142:907–915
Lohmann DR, Fesseler B, Pütz B, Reich U, Böhm J, Wünsch PH, Höfler H (1993b) Infrequent mutations of the p53 gene in pulmonary carcinoid tumors. Cancer Res (in press)
Orita M, Suzuki Y, Sekiya T, Hayashi K (1989) Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5:874–879
Rodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, Lane DP (1990) p53 mutations in colorectal cancer. Proc Natl Acad Sci USA 87:7555–7559
Tamura G, Kihana T, Nomura K, Terada M, Sugimura T, Hirohashi S (1991) Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. Cancer Res 51:3056–3058
Author information
Authors and Affiliations
Additional information
Supported by the European Community contract No. BI-7-0002, Deutsche Forschungsgemeinschaft SFB 207 (F10)
Rights and permissions
About this article
Cite this article
Lohmann, D.R., Funk, A., Niedermeyer, H.P. et al. Identification of p53 gene mutations in gastrointestinal and pancreatic carcinoids by nonradioisotopic SSCA. Virchows Archiv B Cell Pathol 64, 293–296 (1993). https://doi.org/10.1007/BF02915125
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02915125