KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

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

Revista

Título: Oncogene

Vol. 26

Páginas: 158-163

ISSN: 0950-9232

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 139 Citações

Scopus - 145 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6