Multiplex PCR (MPCR) Screening Can Detect Small Intragenic p53 Deletion and Insertion Mutations

Mutations of the p53 tumor suppressor gene are the most common alterations associated with malignancy identified so far. Inactivation of the p53 gene contributes to loss of a cell-cycle check point at the G1-S boundary and to genetic instability of the cell eventually allowing cells to replicate in an uncontrolled fashion (1). Inactivating p53 mutations have frequently been identified in many different forms of cancer including more than 50% of ovarian cancers (2,3). The type and location of p53 mutations occurring in human tumors are nonrandom. In a compilation of more than 4200 p53 mutations in human cancers by Soussi et al., 50% of the mutations were missense mutations, 37% frameshift mutations, and 13% nonsense mutations (4). Small intragenic deletions and insertions have gained little attention in the analyses of the p53 gene in human tumors (5,6). However, a review that compiled 740 p53 mutations from a wide variety of cancers showed that 10% of the mutations were either deletions or insertions (7). Insertions were mostly flanked by short direct repeats of up to 14 basepairs (bp). Deletions of up to 37 bp often occurred in areas of sequence repeats. Such structural changes may be explained by a slipped mispairing mechanism during DNA replication (7).