الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Diffuse large B-cell lymphoma (DLBCL) is a cancer of large B-lymphocytes. It often arises in lymph nodes, but it can primarily arise in extranodal sites in up to 40% of the cases. DLBCL is the single most common type of lymphoma representing approximately 40% of Non-Hodgkin lymphoma cases worldwide. DLBCL is an aggressive type of NHL with a rapidly escalating clinical course.
Diagnosis of DLBCL depends primarily on excisional biopsy of the suspected mass, immunophenotyping by flowcytometry or immunohistochemistry, molecular diagnosis and cytogenetics. PET scan, CT scan and bone marrow examination are important for staging of the disease.
Although DLBCL is potentially curable by current therapeutic strategies, 40% of treated patients are initially refractory to treatment or eventually relapse. Currently, diagnosis and prognosis of DLBCL is based on clinical evaluation, invasive biopsies and PET/CT scans. There’s an urgent need for a noninvasive tool that can give a picture of the original lymphoma to facilitate earlier diagnosis, reliable prognosis, and closer monitoring of the disease. Circulating cell free DNA (cfDNA) was shown to contain circulating tumor DNA; therefore, cfDNA is the promising liquid biopsy in cancer patients that can be retrieved from a simple blood draw.
Cell free DNA circulates in peripheral blood unbound to cells and consists of double stranded DNA fragments. Cell free DNA is either passively released from necrotic or apoptotic cells or actively secreted by cells. Normally, cfDNA is present in the blood of healthy individuals at very low levels and increases only during pregnancy or sometimes post exercise. However, cfDNA levels are greatly increased in patients with malignancies, autoimmune diseases, trauma, myocardial infacrtion, stroke or other inflammatory conditions.
DNA integrity index (DII) describes the size distribution of cfDNA fragments which reflects the source of cfDNA. DII is defined as the ratio between longer and shorter DNA fragments. Fragmentation profiles of cfDNA greatly differ between healthy individuals and cancer patients; therefore, DII of cfDNA has recently been studied as a biomarker of cancer in several studies using several genes or repetitive DNA elements. ALU elements have recently been the most commonly used quantitative PCR target to evaluate DII in several cancers using two primer sets to represent shorter and longer fragments of cfDNA. For example, ALU 247 and ALU 115 primers amplify longer and shorter fragments respectively. ALU elements (Arthrobacter Luteus elements) are short interspersed nuclear elements that are repetitive non-coding DNA sequences with abundant copies in the genome.