97_09_LB_Cancer

97_09_LB_Cancer - Bio 97 Lifetime risk Cancer 1999-2009 Lee...

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1 Cancer ©1999-2009 Lee Bardwell Bio 97 Lifetime risk Chance of developing cancer sometime in your life: Men ~1 in 2 (~ 50%) Women ~ 1 in 3 (~ 33%) 3/4 of all cancers are diagnosed at age 55 and older If you get cancer. .. 5-year survival rate is ~ 60% Cancer is a loss of growth regulation Cells grow when they shouldn’t , forming a tumor Cells grow where they shouldn’t --> invasion, metastasis ©1999 Lee Bardwell
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2 Cancer is a genetic disease of somatic cells • Mutations in specific genes can cause a normal cell to become cancerous ©1999 Lee Bardwell Somatic mutations Occur frequently about 1 mutation/every 3 cell divisions Normally inconsequential Not passed on to next generation Who cares if one cell in your body is “hemophilliac” But if somatic mutations occur in cancer causing genes, you care ©2000 Lee Bardwell What are some of these genes that lead to cancer when mutated? Oncogenes Gas pedal for cell proliferation Mutation --> Gas pedal stuck down Tumor suppressor genes Brakes for cell division Mutation --> Brakes don’t work ©2001 Lee Bardwell Mutations in several distinct genes are required for a normal cell to become cancerous The progressive accumulation of these multiple “hits” explains the age-incidence of cancer ©1999 Lee Bardwell
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3 How do you get cancer? Spontaneous mutations Induced mutations Excessive sunbathing --> UV radiation --> melanoma Cig Smoking --> benzopyrene --> lung cancer ©2001 Lee Bardwell Mutations causing cancer Gross chrm rearrangements Fine-scale Mutations Point mutations (substitutions) Small deletions/duplications/insertions ©2001 Lee Bardwell - Up to 100’s of copies of 50-300 kb region Gene amplification Normal chrm 1 Chrm1 from a neuroblastoma Amplified N-myc gene Abnormal Chromosomes: Cancer Cancer cells are typically aneuploid, with many chrm abberations Some of these are required for tumorigenesis, others provide a selective advantage to the tumor, others are neutral Cancer cells are genetically unstable Philadelphia chromosome t(9;22)(q34;q11) first genetic abnormality linked with a specific type of cancer, chronic myelogenous leukemia (CML) --> deregulation of ABL gene ©1999 Lee Bardwell
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4 Carcinogenesis, tumorigenesis The creation of a cell capable of forming a tumor from a normal cell Tumor progression The progressive “evolution” of a tumor from a more benign to a more malignant state ©1999 Lee Bardwell 13 Malignant versus Benign Tumors Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites Time Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis How to be a successful cancer cell Hanahan, D., and Weinberg, R.A., The Hal marks of Cancer, Cel 100, 57-70 (2000) First requirement Activated Oncogene
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97_09_LB_Cancer - Bio 97 Lifetime risk Cancer 1999-2009 Lee...

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