Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Colorectal cancer (Colorectal Cancer) - BRAF gene.  

Colorectal cancer is one of the most common causes of cancer death, accounting for about 10% of them exceeded only by lung cancer. It is a disease that involves several stages, and mutations in various genes for progression are needed. Mutations in the KRAS gene, a member of the signaling pathway activated protein kinase mitogen, are involved in the development of colorectal carcinoma. On the other hand, the BRAF gene also is mutated in certain colorectal cancers. It is located on the long arm of chromosome 7 (7q34) and encodes a serine / threonine cytoplasmic RAF family, like K-ras is essential member of the signaling pathway kinases mitogen activated protein kinase. Upon activation of RAS, BRAF and MEK phosphorylates and activates ERK.

Oncogenic mutations in the BRAF gene destroy the kinase domain, which results in constitutive activation of mitogen -activated protein explaining the oncogenic potential, given the effects on transcription factors, proliferation and survival activated. They were detected over 30 mutations in the coding sequence of the BRAF gene, but the sequence encoding the kinase domain, in exon 15, there is a "hotspot" hot - spot that has more than 90% of localized mutations in the BRAF gene. The mutation consists of the substitution of valine for glutamic acid molecule at residue 600 (V600E). The protein resulting from this genetic alteration has 10 times more activity than the same protein in normal conditions.

Mutations in the BRAF gene, predominantly at codon 600, are detected in approximately 12-15% of sporadic colorectal cancers and in premalignant lesions such as adenomas, hyperplastic polyps and early stages of development of colorectal cancer. The frequency of changes in the BRAF gene, however, increases in colorectal sporadic cancers with microsatellite instability (MSI) in which the mutational incidence is, according to a recent study, about 91% (compared to 7 % in sporadic colorectal cancers with microsatellite stability -MSS-), in contrast to KRAS mutations which are more common in tumors without microsatellite instability. In fact, mutations in BRAF and KRAS gene are mutually exclusive. This correlation between MSI and genetic alterations in BRAF, however, to cases of hereditary nonpolyposis colorectal cancer (also called HNPCC) -associated with mutations DNA- repair genes which exclude anomalies in BRAF -see not moved Cancer familial colorectal hereditary nonpolyposis (Lynch syndrome ...) - MLH1, MSH2, MSH6 and PMS2-.

Thus, detection of mutations in the BRAF gene reports on the origin of colorectal cancer and is associated with sporadic cancer and allowing rule with a high probability Lynch syndrome. If negative the study of DNA repair genes (MMR: Missmatch Repair genes) can be performed associated with HNPCC -see nonpolyposis colorectal cancer family hereditary (Lynch syndrome ...) - MLH1, MSH2, MSH6 and PMS2-. Knowledge of the origin of colorectal cancer is critical because it allows a better selection of therapy and counseling about the risk of metastasis and prevention opportunities in family.

In some cases, the location of mutations in the BRAF gene can also provide information about prognosis, since its presence is associated with poor prognosis in cases of microsatellite stable (MSS).  

Tests in IVAMI: IVAMI performed in detecting mutations in the BRAF gene, by complete PCR amplification of the gene exons and subsequent sequencing. We suggest starting the study by exon 15, which are located more than 90% of anomalies, thereby reducing time and cost.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).