Introduction
Cancer is the general name for over 100 medical conditions involving uncontrolled and dangerous cell growth.  Some cancer is caused by genetic factors, while other forms are caused by environmental conditions.  The process cancer arise is called oncogenesis.  Tumors are tissue composed of cells that deviate from normal program of cell division and differentiation. There are three types of tumors: benign, malignant and metastasis tumors.   Four major causes: spontaneous gene or chromosomal mutation, exposure to mutagens, exposure to tumor virus, and genetically inherited mutation. 

Cell cycle and cancer
Tumors usually arise from un-restrained cell proliferation, in another word, the cell cycle is abnormal. Many genes controlling cell cycle are also tumor suppressors or oncogenes.  Cancer cells are similar to stem cells in their ability to proliferate unlimitedly and their self-renewal ability.

Oncogene and cancer
Oncogenes stimulate cell growth and proliferation.  The normal cellular gene for such function is called proto-oncogene, when they mutate, usually with higher activity or lost regulation, they become oncogene (c-onc).  These genes can also be derived from RNA tumor virus (v-onc).  DNA tumor viruses do not have oncogenes but they stimulate cell proliferation via inhibiting the cell cycle inhibitors.

Tumor suppressors and Two-hit model
Tumor suppressors are genes that reduce the probability of tumorigenesis. A mutation or deletion of such a gene will increase the probability of the formation of tumor. They inhibit cell division or promote cell death, or both.  Tumor suppressors sometimes require two mutations to lose their function, this is Knudson’s Two-Hit Model.  Haploinsufficiency is exceptional to Two-Hit Model.  For some tumor suppressors when one copy is mutated, the other good cannot fully sustain its normal function.

DNA repair and cancer
DNA repair genes are a group of genes that function in repair damaged DNA and reduce mutations, therefore maintain genome integrity.  When these gene mutate, the mutation rate increase significantly and chance for oncogenesis increase correspondingly.  Some cancer types such as human non-polyposis colon cancer and familial breast cancer is caused by mutations DNA repair genes. 

Normal cell cycle is strictly controlled by a number of genes, cancer cells lost this control.  When cells undergo unrestricted growth and proliferation, tumors arise.  Many genes controlling cell cycle are also tumor suppressors or oncogenes. Oncogenes stimulate cell growth and proliferation, and they are derived from cellular proto-oncogenes.  Tumor viruses cause tumor via oncogene or inhibiting cell cycle inhibitor genes.  The probability of the formation of tumor increases when a tumor suppressor gene mutates. Knudson’s Two-Hit Model proposes that it requires two mutations to lose the function of a tumor suppressor.  However, haploinsufficiency is an exception.  Mutations in DNA repair genes may be direct cause of some cancer types because they increase mutation rate significantly.

• Concept is explained how cancer arises.
• Comparison of cancer cells with stem cells is given.
• Detailed information and diagrams on how oncogenes are derived.
• Diagram explanation of two-hit model.
• Relationship of DNA repair genes and cancer is discussed.

Introduction

• What is cancer
• Oncogenesis and tumor
• Tumor types
• Oncogenesis causes

Cell cycle and cancer

• Overview
• Genes controlling cell cycle
• Cell proliferation vs differentiation
• Stem cells and cancer stem cells
• Signal transduction in cell cycle

Oncogene and cancer

• Overview
• Proto-oncogene
• Viral oncogene and RNA tumor virus
• v-onc vs c-onc
• DNA tumor virus

Tumor suppressor and Two-hit model

• Overview
• Discovery of tumor suppressors
• Two-hit model overview
• Retinoblastoma as an example of two-hit model
• RB and p53 genes as example of tumor suppressors

DNA repair genes and cancer

• Overview
• Human non-polyposis colon cancer and mismatch repair
• Familial breast cancer, BRCA1 and DNA repair