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Detection and assignment of TP53 mutations in tumor DNA using peptide mass signature genotyping

✍ Scribed by Cheryl A. Telmer; Jiyan An; David E. Malehorn; Xuemei Zeng; Susanne M. Gollin; Chandramohan S. Ishwad; Jonathan W. Jarvik

Book ID: 102259612
Publisher: John Wiley and Sons
Year: 2003
Tongue: English
Weight: 153 KB
Volume: 22
Category: Article
ISSN: 1059-7794
DOI: 10.1002/humu.10248

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✦ Synopsis

This report describes the application of a new approach to tumor genotyping called peptide mass signature genotyping (PMSG) that is particularly suited to detecting minority sequences in a DNA sample. Detecting minority sequences is essential for accurate tumor genotyping because tumor resections are generally a mixture of malignant and non-malignant cells, with the mutations of interest often outnumbered by the corresponding wild-type alleles. To explore the suitability of PMSG for tumor genotyping, 25 human squamous cell carcinomas of the head and neck, as well as a set of cell lines derived from those tumors, were analyzed for mutations in exons 5 to 8 of the TP53 gene, the exons that encode the DNA-binding domains of the p53 protein. PMSG identified mutations in 11 tumor DNA samples, whereas dideoxy sequencing of the same samples detected mutations in only four. Currently, PMSG can be used to detect mutations that are present in only 20% of the sample DNA, and we expect that this threshold will be lowered significantly as the PMSG process is improved. Hum Mutat 22:158-165, 2003.

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## Communicated by Mark H. Paalman Mutations in the tumor-suppressor p53 gene TP53 are frequent in most human cancers including breast cancer. A new solid phase chemical cleavage of mismatch method (CCM) allowed rapid and efficient screening and analysis of the TP53 gene in DNA samples extracted