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Ewing Sarcoma Family Tumors PowerPoint Presentation

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Description : Two new gene variants, which each increase the risk of bone marrow cancer by 30 percent, have been identified by scientists at the Institute for Cancer Research. The cancer, known as multiple myeloma, affects the white blood cells of the bone marrow and around 4,000 people in the UK develop it each year. Relatives of patients have four times the chance of developing the disease.

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Published on : Dec 23, 2019 | Views : 1348 | Downloads : 15

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Ewing sarcoma استاد مربوطه :دکتر خاتمی گردآورنده: سید محمد حسین میرصادقی ژنتیک سرطان
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Ewing’s Sarcoma Primitive Neuroectodermal Tumor (PNET) Askin’s Tumor 1 2 3 Ewing Sarcoma Family Tumors . The cell-of-origin is unknown but is presumed to arise from a mesenchymal stem cell. (Bone –87%)
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Epidemiology Ages 5-20 (median 14-15) Caucasian>> Asian> African-American> African Second most common primary bone tumor Slightly more prevalent in males Previous exposure to ionizing radiation
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Distribution of Ewing's sarcoma: Most frequent locations are the large long bones and the pelvis
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Genetics Most common translocation: t(11;22) (q24;q12) EWS-FLI1 Second most common translocations: t(21;22)(q22;q12) EWS-ERG Other translocations: ETV1, E1AF, FEV, or ZSG
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EWS Gene EWS-ETS gene encodes multifunctional protein involved in various cellular processes , including gene expression, cell signalling, and RNA processing and transport. Ewing Sarcoma Break point Region 1 EWS protein: Transcriptional activation domain RNA-binding domain Highly conserved
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FLI1 Gene Belongs to ETS transcription factors Proto-oncogene Role in cellular processes: cell growth and proliferation, differentiation, and survival Expressed in hematopoietic cells Location: 11q24.1 11q24.3
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EWS-FLI1 Fusion Gene Detected in 85-95% of all Ewing sarcomas DNA-binding function of the FLI1 protein + transcription regulation function of the EWS protein Possible mechanism of action is 2-fold: 1. Cell proliferation and survival: PDGFC, IGF1, MYC, CCND-1, NKX2-2 2. Escape from apoptosis/growth inhibition: p21, p57, TGFβRII, IGFBP3
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Diagnosis X-ray: Diaphysis lesions Irregular destruction Chest for metastases CT scan: Extent of cortical destruction Chest for metastases MRI: Tumor response to chemotherapy Staging
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No definitive blood, urine, or serum test Most definitive diagnostic test is a biopsy: Immunohistological stains Fluorescent In Situ Hybridization RT-PCR What part of the tumour should be biopsied? Periphery of the tumour should be biopsied Soft tissue component
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More than 95% of Ewing sarcomas express CD99 (encoded by the MIC2 gene) on their cell membranes. Genetic exchange between chromosomes can cause cells to become cancerous. Most cases of Ewing's sarcoma (85%) are the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11 EWS/FLI functions as the master regulator.Other translocations are at t(21;22) and t(7;22).Ewing's sarcoma cells are positive for CD99 and MIC2, and negative for CD45 Causes The c-myc protooncogene is frequently expressed in Ewing’s
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May also have systemic symptoms: Fever Anemia Weight loss Localized pain and swelling in the affected bone. Pain and soft-tissue swelling ( pain before a mass appear).
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staging No specific staging system for Ewings sarcoma The AJCC staging systems for bone or softtissue sarcomas may be used.
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This is a very early cancer found on the surface of the skin . It is also known as carcinoma in situ Stage 0 Stage I The tumor has not spread to lymph nodes or distant sites Stage IA These are stage I cancers with tumors that are 2 cm or less that have grown into the underlying tissue no deeper than 1 mm Stage IB These are stage I cancers that have invaded deeper than 1 mm and/or are larger than 2 cm
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Stage II The cancer has grown outside the vulva or perineum to the anus or lower third of the vagina or urine It has not spread to lymph nodes or distant sites Stage IIIA Cancer is in the vulva or perineum or both and may be growing into the anus, lower vagina, or lower urine Either it has spread to a single nearby lymph node with the area of cancer spread 5 mm or greater in size it has spread to 1 or 2 nearby lymph nodes with both areas of cancer spread less than 5 mm in size. It has not spread to distant sites Stage IIIB
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Cancer is in the vulva or perineum or both and may be growing into the anus, vagina, or lower urethra Either, the cancer has spread to 3 or more nearby lymph nodes, with all areas of cancer spread less than 5 mm in size The cancer has not spread to distant sites Stage IIIC Cancer is in the vulva or perineum or both and may be growing into the anus, lower vagina, or lower urethra The cancer has spread to nearby lymph nodes and has started growing through the outer covering of at least one of the lymph nodes called extracapsular spread The cancer has not spread to distant sites
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Stage IVA Cancer spread to nearby lymph nodes has caused them to be stuck (fixed) to the underlying tissue or caused open sores (ulceration) Stage IVB It has not spread to distant sites Cancer has spread to distant organs or lymph nodes This is the most advanced stage of cancer
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Time between first symptoms to diagnosis: 2-9 months “Troublesome” age group Localized vs. metastasized tumor survival rates Secondary cancers
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30-40% of patients develop relapse with <20% survival Early relapse – less than 2 years: Consider Changing Chemotherapy Late relapse – more than 2 years: Continue the previously used chemotherapy
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