Human Genetics: Concepts and Applications (Lewis), 9th Edition

Chapter 18: Genetics of Cancer

Chapter Outline

CHAPTER OVERVIEW

1. The term tumor is used for abnormal cell growth that does not invade surrounding tissue.
2. Cancer, or a malignant tumor, spreads locally and usually also metastasizes to distant sites.
3. Carcinogens, most of which are mutagens, are cancer producing agents.
4. The search for cancer genes in families has given way to a genomic approach to identifying oncogenes and anti-oncogenes.
5. More than 100 oncogenes and 30 tumor suppressor genes have been identified.
6. DNA microarrays can be used to identify and distinguish different types of tumors.

1. Cancer is caused by a loss of cell division control.
2. Genes involved in the onset and progression of cancer include those encoding growth factors, transcription factors, DNA repair genes, and telomerase.

1. Several mutations may contribute to the development of cancer.
2. Most cancers are sporadic and therefore, the causative mutation occurs in cells of the affected tissue.
3. Cancer may develop when an environmental trigger causes mutations in a somatic cell or when a somatic mutation compounds an inherited susceptibility.

1. Cancer cells do not respond to normal cell cycle control signals and as a result they grow vigorously and continuously.
2. The cancer phenotype is heritable and transmitted to daughter cells.
3. A cancer cell differs from normal cells in that it is transplantable (can grow in a susceptible animal), dedifferentiated (less specialized), lacks contact inhibition (pile up in culture), and can invade healthy tissue or metastasize to distant sites.

1. Cancer cells have a phenotype that is more specialized than stem cells but less differentiated than normal tissue.
2. This may result from dedifferentiation of a normal cell or the proliferation of cancer stem cells.

1. Mutations in oncogenes, tumor suppressor genes and DNA repair genes can all cause cancer

1. Many genes that normally control the cell cycle are proto-oncogenes.
2. Proto-oncogenes are transformed into oncogenes by genetic changes that increase their expression or alter the biological activity of their protein product.
3. Changes in gene expression levels can be used to diagnose and monitor treatment of cancer.

1. Tumor suppressor genes down regulate cell growth.
2. Deletions of tumor-suppressor genes or other changes, such as hypermethylation, that result in loss of function may lead to cancer.
3. Loss of tumor-suppressor function allows cells to ignore normal constraints on cell division.
4. The RB, p53, and BRCA1 genes are examples of tumor suppressors.

1. MicroRNAs are important in the regulation of oncogenes and tumor suppressor genes at the post-transcriptional level
2. MicroRNA alterations may lead to cancer
3. The relationship between oncogenes, tumor suppressor genes and microRNAs is complex. Understanding the relationship may lead to better diagnosis and treatment of cancer.

1. Most cancers are not the result of alterations of a single oncogene or tumor suppressor gene but involve a series of mutations in several genes.

1. FAP begins in early childhood with precancerous growths called polyps.
2. An autosomal dominant pattern of inheritance is associated with FAP and it occurs with a frequency of one in 5000 people in the United States.
3. A dominant mutation in the APC gene on chromosome 5 is the first step in the multi-step model for FAP colon cancer.
4. Subsequent mutations cause the transformation of the polyp into a tumor.

1. Genome research is revealing common pathways affected in different types of cancer
2. This research aids evaluation of present therapeutic agents and suggests new targets for drugs

1. Epidemiological studies are used to identify risk factors in a population.
2. Many environmental carcinogens have been identified along with factors that lower the risk of cancer. Smoking and excess exposure to the sun are linked with increased risk of cancer.
3. Avoiding fats along with eating more fruits, vegetables, and whole grain cereals is associated with a lower cancer risk.

1. Treatments for cancer target the characteristics of cancer cells.
2. Surgery removes tumors. Chemotherapy and radiation non-selectively destroy rapidly dividing cells.
3. Newer treatments target receptors on cancer cells, block telomerase, trigger redifferentiation, or attack a tumor's blood supply.
4. DNA microarrays and human genome data are being used to diagnose and manage cancer.