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Copyright © 2009 Pearson Education, Inc. Essentials of Genetics Seventh Edition Klug, Cummings, Spencer, Palladino Chapter 16 Cell Cycle Regulation and Cancer Copyright © 2009 Pearson Education, Inc.

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Copyright © 2009 Pearson Education, Inc.

Essentials of GeneticsSeventh EditionKlug, Cummings, Spencer, Palladino

Chapter 16Cell Cycle Regulation and Cancer

Copyright © 2009 Pearson Education, Inc.

Copyright © 2009 Pearson Education, Inc. Table 20.1

16.1 Cancer Is a Genetic Disease That Arises at the Level of Somatic Cells

Copyright © 2009 Pearson Education, Inc.

Figure 16.1a

Spectral karyotype of a normal cell

Copyright © 2009 Pearson Education, Inc.

Figure 16.1b

Spectral karyotype of a cancer cell, showing translocations, deletions, and aneuploidy.

Copyright © 2009 Pearson Education, Inc.

Copyright © 2009 Pearson Education, Inc.

16.1 Cancer Is a Genetic Disease

What Is Cancer? Not a single disease Vary in age of onset, growth rates,

invasiveness, prognoses, and response to treatment.

At molecular level, all cancers exhibit common characteristics

Cell Proliferation = Abnormal cell growth and division

Metastasis = Abnormalities in normal restraints that keep cells from spreading and invading other body parts.

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16.1 Cancer Is a Genetic Disease

The Clonal Origin of Cancer Cells All cancer cells are clonal

Originated from common ancestral cell that accumulated specific mutations.

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16.1 Cancer Is a Genetic Disease

Cancer As a Multistep Process, Requiring Multiple Mutations

A single mutation is not sufficient to transform a normal cell into a tumor forming, malignant cell.

Mutations in humans occur randomly at a rate of 1010 mutations per gene in the body during their lifetime.

Incidence of cancer rises exponentially with age. Many independent mutations, occurring randomly,

are necessary before a cell becomes malignant. Delay occurs between exposure to carcinogens and

the appearance of cancer.

Copyright © 2009 Pearson Education, Inc.Figure 18-2 Copyright © 2006 Pearson Prentice Hall, Inc.

Copyright © 2009 Pearson Education, Inc.

20.2 Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair and Chromatin Modifications

Genomic Instability and Defective DNA Repair• Cancer cells show higher than normal rates of

mutation, chromosomal abnormalities, and genomic instability.

• Cancer cells grown in cultures show a great deal of genomic instability

• Cancers show specific defects that are used to diagnose the type and stage of cancer.

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DNA amplification in neuroblastomaCancer genes are colored and remain separate from chromosomal DNA.

Red = MYCNGreen = MDM2Blue = normal

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Multiple copies of the MYCN gene are amplified in the green staining region; single copies are seen as the small green dots; normal chromosomes are stained red.

Copyright © 2009 Pearson Education, Inc. Figure 20.3

Copyright © 2009 Pearson Education, Inc.

Thursday, November 6, 2008

Scientists Decode Set of Cancer Genes

By DENISE GRADYPublished: November 5, 2008

For the first time, researchers have decoded all the genes of a person with cancer and found a set of mutations that may have caused the disease or aided its progression. Using cells donated by a woman in her 50s who died of leukemia, the scientists sequenced all the DNA from her cancer cells and compared it to the DNA from her own normal, healthy skin cells. Then, they zeroed in on 10 mutations that occurred only in the cancer cells, apparently spurring abnormal growth, preventing the cells from suppressing that growth and enabling them to fight off chemotherapy.

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NYTimes article on new teatment

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16.2 Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair and Chromatin Modifications

Chromatin Modifications and Cancer Epigenetics Epigenetics is the heritable changes that occur to DNA

without affecting the nucleotide sequence of DNA. Cancer cells contain DNA with major methylation

alterations Histone modifications lead to packaging issues related to

DNA organization.

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16.3 Cancer Cells Contain Genetic Defects Affecting Cell-Cycle Regulation

The Cell Cycle and Signal Transduction

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Cyclins and cyclin-dependent kinases (CDKs) control progress through the cell cycle.

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16.3 Cancer Cells Contain Genetic Defects Affecting Cell-Cycle Regulation

Control of Apoptosis Programmed cell death If mistakes are not corrected during progression through

the cell cycle, apoptosis must occur. Nuclear DNA becomes fragmented, the cell dissolves,

and phagocytic cells engulf and destroy. Apoptosis reduces the number of mutations that are

passed to the next generation.

Copyright © 2009 Pearson Education, Inc. Figure 20.8

Copyright © 2009 Pearson Education, Inc.

16.4 Many Cancer-Causing Genes Disrupt Control of the Cell Cycle

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16.4 Many Cancer-Causing Genes Disrupt Control of the Cell Cycle

The ras Proto-oncogenes

Copyright © 2009 Pearson Education, Inc.Figure 18-12 Copyright © 2006 Pearson Prentice Hall, Inc.

Copyright © 2009 Pearson Education, Inc.

16.4 Many Cancer-Causing Genes Disrupt Control of the Cell Cycle

The cyclin D1 and cyclin E Proto-oncogenes

The p53 Tumor-Suppressor Gene

The “guardian of the genome”

The RB1 Tumor-Suppressor Gene

Copyright © 2009 Pearson Education, Inc. Figure 20.10

Copyright © 2009 Pearson Education, Inc. Figure 20.11

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Predisposition to Some Cancers Can Be Inherited

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20.7 Viruses Contribute to Cancer in Both Humans and Animals

Copyright © 2009 Pearson Education, Inc. Figure 20.13

Copyright © 2009 Pearson Education, Inc.

20.8 Environmental Agents Contribute to Human Cancers

Obesity responsible for 100,000 cancer cases annually

By Matt Sloane, CNN Medical NewsNovember 5, 2009 5:58 p.m. EST