Caring for Carcinoid Foundation - Genetic Research Paradigm

The genetic research paradigm enables scientists to discover a cure for cancer by unlocking its genetic causes, then developing novel, targeted therapies.

In the past, scientists had to take “blind aim” at treating cancer because they lacked a genetic understanding of its causes. Now, we live in a tremendously exciting time for cancer research due to the completion of the Human Genome Project in 2003. This major advance in genetic knowledge has enabled scientists to study cancer—including carcinoid—at the level of individual genes and develop highly effective, targeted treatments.

The following presentation was prepared by the National Cancer Institute. It provides an overview of the genetic research paradigm and why it is now possible to discover a cure for cancer, including carcinoid.

For further information, please review the references listed at the end.

Slide 1: Genetic mutations lead to cancer
Slide 2: What is a gene?
Slide 3: What is DNA?
Slide 4: DNA à RNA à Protein
Slide 5: Genetic mutations and disease
Slide 6: Types of genetic mutations
Slide 7: Altered DNA à altered protein
Slide 8: Acquired mutations
Slide 9: Hereditary mutations
Slide 10: Microarray analysis
Slide 11: Human Genome Project
References

Slide 1: Genetic mutations lead to cancer

All cancer is genetic, in that it is triggered by altered genes. Genes that control the orderly replication of cells become damaged, allowing the cells to reproduce without restraint.
Cancer usually arises in a single cell. The cell’s progress from normal to malignant to metastatic appears to involve a series of distinct changes in the tumor and its immediate environment, and each is influenced by different sets of genes.

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Slide 2: What is a gene?

A gene is a working subunit of a DNA molecule.
A gene is any given segment along the DNA carrying a particular set of instructions that allows a cell to produce a specific product—typically, a protein such as an enzyme. There are about 25,000 genes, and every gene is made up of thousands, even hundreds of thousands, of chemical bases.

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Slide 3: What is DNA?

DNA is a vast chemical information database. It resides in the core, or nucleus, of each of the body’s trillions of cells, and it carries the complete set of instructions for making all the proteins a cell will ever need.

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Slide 4: DNA à RNA à Protein

Building proteins lies at the heart of cell function.
For a cell to make a protein, the information from a gene is copied, base by base, from a strand of DNA into a strand of messenger RNA. Messenger RNA travels out of the nucleus into the cytoplasm, to cell organelles called ribosomes. There, messenger RNA directs the assembly of amino acids that fold into a completed protein molecule.

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Slide 5: Genetic mutations and disease

A sound body depends on the continuous interplay of thousands of proteins, acting together in just the right amounts and in just the right places—and each properly functioning protein is the product of an intact gene.
Many, if not most, diseases have their roots in our genes. More than 4,000 diseases stem from altered genes inherited from one’s mother and/or father. Common disorders such as heart disease and most cancers arise from a complex interplay among multiple genes and between genes and factors in the environment.

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Slide 6: Types of genetic mutations

Genes can be altered, or mutated, in many ways.
The most common gene change involves a single base mismatch—a misspelling—placing the wrong base in the DNA. At other times, a single base may be dropped or added. And sometimes large pieces of DNA are mistakenly repeated or deleted.

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Slide 7: Altered DNA à altered protein

When a gene contains a mutation, the protein encoded by that gene is likely to be abnormal.
Sometimes the protein will be able to function, but imperfectly. In other cases, it will be totally disabled. The outcome depends not only on how it alters a protein’s function but also on how vital that particular protein is to survival.

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Slide 8: Acquired mutations

Acquired mutations are changes in DNA that develop throughout a person’s lifetime.
Although mistakes occur in DNA all the time, especially during cell division, a cell has the remarkable ability to fix them. But if DNA repair mechanisms fail, mutations can be passed along to future copies of the altered cell.

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Slide 9: Hereditary mutations

Gene mutations can be either inherited from a parent or acquired.
Hereditary mutations are carried in the DNA of the reproductive cells. When reproductive cells containing mutations combine to produce offspring, the mutation will be in all of the offspring’s body cells. The fact that every cell contains the gene change makes it possible to use cheek cells or a blood sample for gene testing.
Even though all cancer is genetic, just a small portion—perhaps 5 or 10 percent—is inherited.
Most cancers come from random mutations that develop in body cells during one’s lifetime—either as a mistake when cells are going through cell division or in response to injuries from environmental agents such as radiation or chemicals.

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Slide 10: Microarray analysis

Much of the excitement today centers on gene expression profiling that uses a technology called microarrays. A DNA microarray is a thin-sized chip that has been spotted at fixed locations with thousands of single-stranded DNA fragments corresponding to various genes of interest. A single microarray may contain 10,000 or more spots, each containing pieces of DNA from a different gene. Fluorescent-labeled probe DNA fragments are added to ask if there are any places on the microarray where the probe strands can match and bind. Complete patterns of gene activity can be captured with this technology.

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Slide 11: Human Genome Project

Identifying genes associated with disease—indeed, tracking down every chemical base in each of the estimated 25,000 genes as well as the spaces between them, a process called mapping the human genome—has been accomplished successfully by an international collaboration known as the Human Genome Project.
Scientists have developed a consensus sequence, laying out the order in which all the human genes sit along the chromosomes. This information can be used to determine where gene mutations occur in specific diseases. For example, here is a chart of disease-linked genes located along the X chromosome.

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References

To learn more about the genetic research paradigm, the Caring for Carcinoid Foundation recommends the following websites:

Department of Energy - Office of Science

"The Department of Energy’s Office of Science founded the Human Genome Project and is a leader in systems biology research."

Website

National Cancer Institute

"The National Cancer Institute (NCI) is a component of the National Institutes of Health, one of eight agencies that compose the Public Health Service in the Department of Health and Human Services. The NCI, established under the National Cancer Act of 1937, is the federal government’s principal agency for cancer research and training."

Website
Document, "Targeted Cancer Therapies: Questions and Answers"

National Center for Biotechnology Information

"As a national resource for molecular biology information, the National Center for Biotechnology Information’s mission is to develop new information technologies to aid in the understanding of fundamental molecular and genetic processes that control health and disease."

Website

National Human Genome Research Institute

"The National Human Genome Research Institute (NHGRI) led the Human Genome Project for the National Institutes of Health, which culminated in the completion of the full human genome sequence in April 2003. Now, the NHGRI moves forward into the genomic era with research aimed at improving human health and fighting disease."

Website
Document, "Genetics - The Future of Medicine"