Rapid diagnosis of germline p53 mutation using the enzyme mismatch cleavage method

The p53 tumor suppressor gene is the most commonly altered gene in human cancers. Germline mutations in p53 are the genetic alteration underlying predisposition to multiple cancers in Li-Fraumeni syndrome and Li-Fraumeni-like syndrome. We describe a patient who presented with developed adrenocortical carcinoma at age 19 months and a cerebral primitive neuroectodermal tumor at age 5 years. The patient did not have a family history of cancer. We used the enzyme mismatch cleavage (EMC) method to screen for mutations in the p53 gene and found a germline mutation in exon 7 (codon 248). Loss of heterozygosity analysis in one tumor revealed loss of the wild-type p53 allele. In our report we demonstrate the EMC method to be a rapid and sensitive method for mutation detection.