Non-Hodgkin family (Non-Hodgkin lymphoma familial) - Genes RAD54L, CASP10, Rad54B and PRF1.
The non-Hodgkin 's family (NHL) is a group of cancers of lymphocytes. In the NHL, lymphocytes are not properly developed, so they can not fight infection effectively. These altered cells multiply very fast and occupy the entire space of leukocytes, erythrocytes and platelets which the body needs. The NHL usually appears in the lymph nodes or lymphatic tissue found in organs such as the stomach, intestines or skin. In some cases NHL involves bone marrow and blood. The lymphoma cells may develop in one or more parts of the body. This disease can occur at any age and often characterized by enlarged lymph nodes, fever and weight loss.
They have identified approximately 60 subtypes of NHL depending on the rate of disease progression. Diffuse lymphoma enlarged B cell lymphoma (DLBCL) is the most common type of aggressive NHL and represents between 30% and 40% of all cases. As regards indolent NHL, follicular lymphoma (FL) is the most common type. The two most common subtypes of NHL, diffuse B - cell lymphoma and follicular lymphoma enlarged, are examples of B cell lymphomas Furthermore, approximately 15% of cases of NHL are affected "T cells" lymphocytes called or "natural killer cells". Among the T cell lymphomas peripheral T cell lymphoma and cutaneous cells include T.
This may be due to mutations in RAD54L, CASP10, Rad54B and PRF1 genes.
The RAD54L gene, located on the short arm of chromosome 1 (1p32), encodes a protein that plays a role in homologous recombination repair related breaks dsDNA. The binding of this protein to dsDNA induces DNA topological change, which is intended to facilitate cutting and stimulate DNA homologous DNA recombination.
The CASP10 gene, located on the long arm of chromosome 2 (2q33-q34), encodes a protein involved in the activation cascade responsible for the execution of apoptosis caspases. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, which dimerize to form active enzyme. This protein is cleaved and active caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations have been identified in the gene CASP10 prodomain coding regions, in the large subunit p17 protease, and the small subunit protease p12. Mutations in the gene CASP10 inactivate gene function, which can lead to loss of its apoptotic function.
The Rad54B gene, located on the long arm of chromosome 8 (8q22.1), encodes a protein involved in DNA repair and mitotic recombination. This protein binds to double stranded DNA, and shows ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, suggesting an active role in meiotic recombination and mitotic.
PRF1 gene, located on the long arm of chromosome 10 (10q22), encodes a protein called perforin. This protein is found in cells called T lymphocytes and natural killer (NK) cells, which destroy other cells. Perforin is involved in the process of cytolysis and regulation of the immune system. This protein is a major component of cytolytic granules within T cells and NK cells. One of the main ways in which T cells and NK cells kill other the cells is to transport and secrete these cytolytic granules containing proteins cell killing on the membranes of target cells. Perforin helps create a channel through the membrane, allowing cytolytic proteins enter the cell and cause their destruction. This cytolytic mechanism also helps regulate the immune system by destroying unneeded T cells. Control the number of T cells prevents immune cytokine overproduction leading to inflammation and, in excess, causing tissue damage. Mutations in the gene PRF1 impair the ability of immune cells to destroy abnormal system, allowing them to grow and divide uncontrollably leading to the onset of cancer.
Although there is some familial association in the disease, most cases of non-Hodgkin 's lymphoma family (NHL) are sporadic and not inherited.
Tests in IVAMI: in IVAMI perform the detection of mutations associated with lymphoma familial non-Hodgkin 's lymphoma (NHL), by complete PCR amplification of the exons of RAD54L, CASP10, Rad54B and PRF1, respectively genes, and subsequent sequencing.
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).