Detection of KRAS, BRAF, PIK3CA and EGFR gene mutations in colorectal carcinoma / 中华病理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mutation frequencies of KRAS, BRAF, PIK3CA and EGFR genes that were effective on the targeted therapies in colorectal carcinoma.</p><p><b>METHODS</b>The tissue specimens from 331 colorectal cancer patients were collected and subject to KRAS, BRAF, PIK3CA and EGFR mutation analysis. Paraffin-embedded tissue samples were obtained and macrodissection was performed to enrich the tumor cells for DNA extraction when necessary. PCR-based direct DNA sequencing was used to investigate the codons 12 and 13 in exon 2 of KRAS gene, exons 11 and 15 of BRAF gene, exons 9 and 20 of PIK3CA gene and exons 18-21 of EGFR gene.</p><p><b>RESULTS</b>Activating mutations were detected in KRAS (44.1%, 137/311), BRAF (5.8%, 9/156), PIK3CA (2.6%, 4/156) and EGFR (1.3%, 2/156) in the study cohort of colorectal carcinoma cases. Among KRAS gene mutations, 81.0% (111/137) occurred in codon 12, with p.G12D as the most common variant (45.3%, 62/137); 19.0% (26/137) occurred in codon 13, with 38G > A (G13D) as the most common variant (17.5%, 24/137).</p><p><b>CONCLUSIONS</b>The KRAS mutation frequency is the highest among the four genes (KRAS, BRAF, PIK3CA and EGFT) tested in colorectal carcinoma. The presence of these gene mutations may provide therapeutic information for targeted therapy. Mutation analyses of BRAF and PIK3CA in addition to KRAS should be a part of the standard diagnostic algorithm for colorectal carcinoma patients.</p>