A double germline mutations in the APC and p53 genes.
Germline mutation in the APC gene is required for the initiation of the development of familial adenomatous polyposis (FAP). According to Fearon and Vogelstein model, further somatic mutations in the K-ras oncogene, DCC gene and p53 tumor suppressor gene are prerequisite for development of colon carcinoma. We have found that the germline mutations in the DNA isolated from lymphocytes of an 18 years old girl with extraordinary expressive phenotype in codons 1060-1061 of the APC gene result in truncation of the APC protein. The mutation in codons 12 and 13 of the K-ras oncogene was not detected, but another germline mutation was found in codon 210 of the p53 gene. Furthermore, no one of these germline mutations was detected in the DNA of peripheral blood lymphocytes of the patient's 21 years old healthy sister. Until now, there has been no evidence about the expressive phenotype due to mutation in codons 1060-1061 of the APC gene; the role of germline missense mutation in codon 210 of the p53 gene in the FAP malignant process remains to be elucidated too. The effect of the combination of germline mutation in two different tumor suppressor genes in the progress of disease is discussed.
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic. exonvzaj@savba.sk
V
V
Zajac
M
M
Tomka
D
D
Ilenciková
P
P
Májek
V
V
Stevurková
T
T
Kirchhoff
D011125:Adenomatous Polyposis Coli / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein; D000293:Adolescent; D000328:Adult; D000483:Alleles; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D018095:Germ-Line Mutation; D020180:Heteroduplex Analysis; D006801:Humans; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000235:genetics
D025601:Adenomatous Polyposis Coli Protein; D003062:Codon; D003598:Cytoskeletal Proteins