Combined analysis of specific KRAS mutation, BRAF and microsatellite instability identifies prognostic subgroups of sporadic and hereditary colorectal cancer
✍ Scribed by Inti Zlobec; Michal Kovac; Priska Erzberger; Francesca Molinari; Michel P. Bihl; Alexander Rufle; Anja Foerster; Milo Frattini; Luigi Terracciano; Karl Heinimann; Alessandro Lugli
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- French
- Weight
- 421 KB
- Volume
- 127
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Confounding effects of specific KRAS gene alterations on colorectal cancer (CRC) prognosis stratified by microsatellite instability (MSI) and BRAF^V600E^ have not yet been investigated. The aim of our study was to evaluate the combined effects of MSI, BRAF^V600E^ and specific KRAS mutation (Gly → Asp; G12D, Gly → Asp, G13D; Gly → Val; G12V) on prognosis in 404 sporadic and 94 hereditary CRC patients. MSI status was determined according to the Bethesda guidelines. Mutational status of KRAS and BRAF^V600E^ was assessed by direct DNA sequencing. In sporadic CRC, KRAS G12D mutations had a negative prognostic effect compared to G13D and wild‐type cancers (p = 0.038). With MSI, specific KRAS and BRAF^V600E^ mutations, 3 distinct prognostic subgroups were observed in univariate (p = 0.006) and multivariable (p = 0.051) analysis: patients with (i) KRAS mutation G12D, G12V or BRAF^V600E^ mutation, (ii) KRAS/BRAF^V600E^ wild‐type or KRAS G13D mutations in MSS/MSI‐L and (iii) MSI‐H and KRAS G13D mutations. Moreover, none of the sporadic MSI‐H or hereditary patients with KRAS G13 mutations had a fatal outcome. Specific KRAS mutation is an informative prognostic factor in both sporadic and hereditary CRC and applied in an algorithm with BRAF^V600E^ and MSI may identify sporadic CRC patients with poor clinical outcome.