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Cancer Genetics دکتر منصور صالحی 1) گروه ژنتیک، دانشکده پزشکی، علوم پزشکی اصفهان

Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran. Cancer Genetics دکتر منصور صالحی 1) گروه ژنتیک، دانشکده پزشکی، علوم پزشکی اصفهان 2) آزمایشگاه ژنتیک بیمارستان الزهرا (س) 3) مرکز ژنتیک پزشکی ژنوم.

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Cancer Genetics دکتر منصور صالحی 1) گروه ژنتیک، دانشکده پزشکی، علوم پزشکی اصفهان

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  1. Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

  2. Cancer Genetics دکتر منصور صالحی 1) گروه ژنتیک، دانشکده پزشکی، علوم پزشکی اصفهان 2) آزمایشگاه ژنتیک بیمارستان الزهرا (س) 3) مرکز ژنتیک پزشکی ژنوم

  3. Why cancer genetics? 1 in 4 deaths is due to cancer More than half of the population will be diagnosed with invasive cancer at some point in their lives Many cancers are increasing in frequency; Why? Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  4. Cancer cells typically contain multiple alterations in the number and structure of genes and chromosomes

  5. Cells are programmed to develop, growth, differentiate and die  SIGNALS Signals: - Growth factors - Steroid Hormones - Cell-Cell interaction Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  6. Cancer Genes Genetic control of cell growth and differentiation Cancer causing genes  more than 200

  7. Growth factors:- Platelet Derived Growth Factor- Epidermal Growth Factor- Hepatocyte Growth Factor- Lipid Molecules- Steroid Hormones- Cell-Cell Contacts- Cell-Matrix interaction

  8. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University of Medical School

  9. Effect of hepatocyte growth factor (HGF) on the level of Survivin & XIAP expression in several human cancer cell lines, after treating with DNA damaging agent. Mol Cell Biochem. 2007;304(1-2):199-205. Keyhanian K, Edalat R, Oghalaei A, Askary N, Golshani A, Salehi M,Sarrami-Forooshani R, Shokrgozar MA. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  10. Bcl-2 associated gene-1 (Bag1) overexpression in diffuse large B-cell lymphoma. Iran J Immunol. 2008 Jun;5(2):124-30. Ataollahi M, Salehi M, Doostan I, Kabiri Z, Mohajeri M, Mahmoodi F, Shokouhi R, Javan S, Meshkibaf MH, Miladpoor B. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  11. Evaluation of ARG protein expression in mature B cell lymphomas compared to non-neoplastic reactive lymph node Cell Immunol. 2009;259(2):111-6 Kabiri Z, Salehi M, Mokarian F, Mohajeri MR, Mahmoodi F, Keyhanian K, Doostan I, Ataollahi MR, Modarressi MH. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  12. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  13. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  14. Knudson (1971)Retinoblastoma study • Inherited  Bilateral • Non-inherited (sporadic)  Unilateral ↓ Two - hit model of carcinogenesis Is the target of second hit the normal copy of RB gene or it could be anywhere else in the genome?

  15. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  16. Tumour Suppressor Genes in cancerA group of genes that suppress tumour Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  17. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  18. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  19. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  20. Examples of important Tumour Suppressor Genes in cancers Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  21. BRCA1andBRCA2are the most common genes related tohereditary breast cancerMutationsin these geneshigh risk of developing breast cancerand several other types of cancer

  22. Functions of BRCA proteins in response to DNA damage. On DNA damage, BRCA proteins interact with numerous other proteins to modulate DNA repair

  23. Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  24. The most common hereditary colon cancerHereditary nonpolyposis colorectal cancer (HNPCC) ~10% of all colorectal cancers

  25. HNPCC is caused by germline mutations in genes from the DNA mismatch repair (MMR) system Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  26. Genes involvedAt least 5 mismatch repair genes in HNPCCMLH1 on 3p21*MSH2 on 2p16*MSH6 on 2p16PMS1 on 2q32PMS2 on 7p22*( high mutation frequency in HNPCC) Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  27. Two novel mutations in hMLH1 gene in Iranian hereditary non-polyposis colorectal cancer patients. Fam Cancer. 2012 Mar;11(1):13-7. Shahmoradi S, Bidmeshkipour A, Salamian A, Emami MH, Kazemi Z, Salehi M. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  28. Association between Mismatch Repair Gene MSH3 codons 1036 and 222 Polymorphisms and Sporadic Prostate Cancer in the Iranian Population. Asian Pac J Cancer Prev. 2012;13(12):6055-7. Salehi M, Sedghi M, Nouri N, Jafary F, Sadeghi F, Motamedi S, Talebi M. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  29. TP53 PIN3 polymorphism associated with breast cancer risk in Iranian women Indian J Cancer. 2011 Jul-Sep;48(3):298-302 Faghani M, Ghasemi FM, Nikhbakht M, Salehi M. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  30. Missense and nonsense mutations of p53 gene in patients with colorectal adenocarcinoma in Isfahan, central Iran. Iran Red Crescent Med J. 2011 Mar;13(3):215-6. Golmohammadi R, Namazi MJ, Nikbakht M, Salehi M. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  31. Oncogenes - Originate from: Proto-oncogenes- Member of cell signaling pathway- Mostly somatic mutations- No gremlin mutation (sporadic)- Dominant at cellular level Dr. M. Salehi, Dept. of Genetics and Molecular Biology, Isfahan University Medical School

  32. Apoptosis inhibition or inflammation: the role of NAIP protein expression in Hodgkin and non-Hodgkin lymphomas compared to non-neoplastic lymph node. J Inflamm (Lond). 2012 Feb 23;9(1):4 Mazrouei S, Ziaei A, Tanhaee AP, Keyhanian K, Esmaeili M, Baradaran A, Salehi M. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  33. Systematic DNA sequencing - estimates of- hundreds to thousands of point mutations in some tumors

  34. Certainly, 20 or more chromosomal aberrations detectable by cytogenetic techniques are not unusual in an advanced carcinoma. It is therefore very appropriate to regard cancer as a genetic disease

  35. Point mutations Splice mutations Alternative splicing Mutations in regulatory sequences Deletions Insertions Viral genomes Chromosomal translocations Chromosomal inversions Polyploidy and aneuploidy Numerical chromosomal aberrations Gene amplification Structural chromosomal aberrations

  36. Detection of Philadelphia Chromosome (BCR / ABL) by FISH Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  37. epigenetic changes in Cancer Epigenetics: stableinheritance of alterations in gene expression without changes in DNA sequence.

  38. Study of promoter methylation pattern of 14-3-3 sigma gene in normal and cancerous tissue of breast: A potential biomarker for detection of breast cancer in patients. Adv Biomed Res. 2012;1:80. Gheibi A, Kazemi M, Baradaran A, Akbari M, Salehi M. Dr Mansoor Salehi, Dept of Genetics and Molecular Biology, Medical School, IUMS

  39. New approaches to the genetic basis of cancer Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

  40. Non-Coding RNAs (microRNA) in Cancer as Biomarkers in Human Cancers Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

  41. MicroRNAs are small 19- to 25-nucleotide genes involved in regulating gene expression Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

  42. microRNAs are causally involved in the initiation, progression and metastases of human cancers Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

  43. directly targeting miRNAs or Possible use of miRNAs or compounds interacting with miRNAs as new therapeutic agents in cancer patients

  44. A microRNA Assay that Differentiates Pancreatic Ductal Adenocarcinoma from Chronic Pancreatitis 95.24% sensitivity, 94.87% specificity (miR-196a and miR-217 ) Pharmacogenomics Services, Asuragen, Inc. Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

  45. Associations between stem cells and cancer Cancer Stem Cells

  46. Cambridge Healthtech Institute's Third AnnualTargeting Cancer Stem CellsNew Opportunities for Oncology TherapeuticsFebruary 13-14, 2014 - San Francisco, CA - Bringing CSC-targeting compounds to the clinic  - Latest results from the clinic for advanced candidates

  47. Myriad Releases Three New Tests myPath, Melanoma myRisk, Hereditary Cancer myPlan, Lung Cancer Dr. Mansoor Salehi, Dept. of Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

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