KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Oliveira, C (Author) Other; Velho, S (Author) Other; Moutinho, C (Author) Other; Ferreira, A (Author) Other; Preto, A (Author) Other; Domingo, E (Author) Other; Capelinha, AF (Author) Other; Duval, A (Author) Other; Hamelin, R (Author) Other; Machado JC (Author) FMUP; Schwartz, S (Author) Other; Carneiro F (Author) FMUP; Seruca, R (Author) FMUP

Journal

Title: Oncogene

Vol. 26

Pages: 158-163

ISSN: 0950-9232

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 139 Citations

Scopus - 145 Citations

Other information

Authenticus ID: P-004-C9C

DOI: 10.1038/sj.onc.1209758

Abstract (EN): In sporadic colorectal cancer (CRC), KRAS are alternative to BRAF mutations and occur, respectively, in 30 and 10% of cases. Few reports addressed the association between KRAS - BRAF mutations and tumour progression specifically in sporadic microsatellite-stable (MSS) CRC. We screened KRAS and BRAF in 250 MSS primary CRC and 45 lymph node (LN) metastases and analysed the pathological features of the cases to understand the involvement of KRAS - BRAF activation in progression and metastasis. Forty-five per cent of primary MSS CRCs carried mutations in at least one of these genes and mutations were associated with wall invasion (P = 0.02), presence and number of LN metastases (P = 0.02 and P = 0.03, respectively), distant metastases (P = 0.004) and advanced stage (P = 0.01). We demonstrated that KRAS and BRAF are alternative events in Tis and T1 MSS CRC and, KRAS rather than BRAF mutations, contributed to the progression of MSS CRC. The frequency of KRAS and/or BRAF mutations was higher in LN metastases than in primary carcinomas (P = 0.0002). Mutated LN metastases displayed KRAS associated or not with BRAF mutations. BRAF mutations were never present as a single event. Concomitant KRAS and BRAF mutations increased along progression of MSS CRCs, suggesting that activation of both genes is likely to harbour a synergistic effect.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6