Cancer

All cells have the capacity to become cancerous Misusing Normal Tools Using Abnormal “super tools” or “broken tools” All cells have the capacity to become cancerous

Cancers are categorized

Categorization of Cancers Sarcoma Carcinoma

Blood Cancers Myeloid Leukemias Lymphoid Leukemias

Neural Tissue Cancers

Cancers develop gradually

normal metaplasia

Hyperplasia

Pre-Cancer

Epithelial  Mesenchymal Transition (EMT)

Metastasis

Cancers don’t affect everyone equally

Genes altered in cancer typically: Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity

Cancers result from alternations in DNA structure or utilization Sometimes the DNA is mutated, and other times it’s not…

Genes altered in cancer typically: Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity

Genes altered in cancer typically: Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity

Proto-oncogenes  Oncogenes

Conversion of a Proto-oncogene  an Oncogene Change gene expression / Change protein production (Produce TOO MUCH)

Increase promoter utilization by HYPO-METHYLATION

Increase promoter utilization by POINT MUTATION

Alter the promoter that is used by TRANSLOCATION Chromosome 14 with translocation Chromosome 8 with translocation

(by transcription or by stabilization) Increase the amount of mRNA (by transcription or by stabilization) Transcription Translation

Increase the number of copies of a gene

Decrease Turnover

Conversion of a Proto-oncogene  an Oncogene Change the function of a gene product (Produce a “super tool”)

DNA Point Mutation

DNA Deletion / Protein Truncation

Chromosomal Translocation

Genes altered in cancer typically: Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity

Tumor Suppressor Genes

Inactivation of a Tumor Suppressor Gene Change gene Expression

Decrease promoter utilization by HYPER-METHYLATION

Decrease promoter utilization by HYPER-METHYLATION

Decrease promoter utilization by POINT MUTATION N C N C N C No TF SP-1 AP-2 Decrease promoter utilization by POINT MUTATION

Loss of Tumor Suppressor gene function Change gene function (Produce a “broken tool”)

2 x 1 / 106 = 1012 1 / 106

Loss of Heterozygosity: Heterozygote becomes homozygous by some mechanism Loss of an allele (i.e., hemizygosity)

Inactivating mutation Point mutation Insertion Deletion Frameshift