Adenocarcinoma lung (Lung adenocarcinoma) - EGFR and KRAS Genes  

Adenocarcinoma, forms one of the three subtypes of cancer NSCLC (Non-Small Cell Lung Cancer). This type of lung cancer arises from the cells lining the alveoli located in the lungs. It occurs mainly in current or former smokers, but it is also the most common type of lung cancer seen in nonsmokers. It is more common in women than in men, and is more likely to occur in younger people compared to other types of lung cancer. This type of cancer tends to grow more slowly than other types of lung cancer, and is more likely to be detected before it has spread outside the lung. About 40% of lung cancers are adenocarcinomas.

Lung adenocarcinoma may be due to mutations in a variety of genes. including EGFR and KRAS. In addition to these genes they have been identified other related lung cancer genes, among which include AKT1, ALK, BRAF, DDR2, EGFR, ERBB2, MAP2K1, NRAS, PIK3CA, PTEN, and ROS1 RET.

The EGFR gene, located on the short arm of chromosome 7 (7p12), encodes a protein called the epidermal growth factor receptor (EGFR: Epidermal Growth Factor Receptor). This protein across the cell membrane, so that one end of the protein remains inside the cell and the other end remains outside of the cell surface. When these proteins are activated by binding to other molecules, signaling pathways within cells that promote growth and cell division and cell survival they are activated. So far, we have identified at least 10 mutations in the EGFR gene associated with lung cancer. The mutations described so far have been: missense mutations (7), regulatory mutations (1) and repeating variations (2). Almost all EGFR gene mutations are somatic and are present in cancer cells. Somatic mutations in the EGFR gene occurs more frequently in adenocarcinoma. These mutations are more common in people with the disease who have never smoked. Most somatic mutations of EGFR gene are associated with lung cancer removed genetic material in exon 19 or change nucleotides in exon 21. These changes in genes give rise to a receptor protein constitutively active even when not connected to a ligand. As a result, cells constantly proliferate and survive, leading to tumor formation.

21 described mutations in the KRAS gene, located on the short arm of chromosome 12 (12p12.1), of which 20 are nonsense mutations and one is a regulatory mutation. Such alterations are located in codons 12 and 13, which increase the affinity for GTP and at codons 59 and 61, that inactivate the GTPase function autocatalytic. Under normal conditions, the RAS proteins are found in equilibrium between the active form, together with GTP, and the inactive form, bound to GDP. However, mutated forms of RAS lose the ability to hydrolyze GTP and always remain in its active form. As a result, uncontrolled cell proliferation mediated cell cycle in steady state synthesis, favoring tumor development appears.

Most cases of lung cancer are not related to changes in the genes inherited. These cancers are associated with somatic mutations that occur only in certain cells in the lung. When lung cancer is related to changes in inherited genes, the risk of developing cancer is inherited in an autosomal dominant, which means that a copy of the altered in every cell gene is sufficient to increase the likelihood of developing cancer in a person. It is important to note that people inherit an increased risk of developing cancer, not the disease itself. Not all people who inherit mutations in these genes will develop lung cancer.

Tests in IVAMI: in IVAMI perform detection of mutations associated conadenocarcinoma lung, by complete PCR amplification of the exons of EGFR and KRAS, or other of the many genes involved respectively, and subsequent sequencing.

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