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    CANCER

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    Ej Ramos
    Cancer is caused by uncontrolled cell growth that spreads throughout the body. Changes to DNA, known as genetic mutations, cause cells to divide uncontrollably and form tumors. Mutations can be inherited but are usually acquired during one's lifetime. There are over 200 types of cancer that form in different organs and tissues. Risk factors include age, lifestyle, environment, and genetics. The majority of cancers are due to external causes like ultraviolet radiation, tobacco smoke, viruses, and carcinogens.

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    CANCER

    Uploaded by

    Ej Ramos
    7 views45 pages
    Cancer is caused by uncontrolled cell growth that spreads throughout the body. Changes to DNA, known as genetic mutations, cause cells to divide uncontrollably and form tumors. Mutations can be inherited but are usually acquired during one's lifetime. There are over 200 types of cancer that form in different organs and tissues. Risk factors include age, lifestyle, environment, and genetics. The majority of cancers are due to external causes like ultraviolet radiation, tobacco smoke, viruses, and carcinogens.

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    Cancer is caused by uncontrolled cell growth that spreads throughout the body. Changes to DNA, known as genetic mutations, cause cells to divide uncontrollably and form tumors. Mutations can be inherited but are usually acquired during one's lifetime. There are over 200 types of cancer that form in different organs and tissues. Risk factors include age, lifestyle, environment, and genetics. The majority of cancers are due to external causes like ultraviolet radiation, tobacco smoke, viruses, and carcinogens.

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    © All Rights Reserved
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    Download as pptx, pdf, or txt
    7 views45 pages

    CANCER

    Uploaded by

    Ej Ramos
    Cancer is caused by uncontrolled cell growth that spreads throughout the body. Changes to DNA, known as genetic mutations, cause cells to divide uncontrollably and form tumors. Mutations can be inherited but are usually acquired during one's lifetime. There are over 200 types of cancer that form in different organs and tissues. Risk factors include age, lifestyle, environment, and genetics. The majority of cancers are due to external causes like ultraviolet radiation, tobacco smoke, viruses, and carcinogens.

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    © All Rights Reserved
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    of 45

    Cancer

    What is cancer?
    • All cancers derive from single cells that
    have acquired the characteristics of
    continually dividing in an unrestrained
    manner and invading surrounding
    tissues.
    • Cancer cells behave in this abnormal
    manner because of changes in the DNA
    sequence of key genes, which are
    known as cancer genes. Therefore all
    cancers are genetic diseases. Human melanoma cell undergoing cell division
    Credit: Paul Smith & Rachel Errington, Wellcome Images
    Cancer is a disease that spreads throughout the
    body due to uncontrolled cell division. Changes in
    DNA are the cause of cancer. The majority of
    cancer-causing DNA changes take place in parts
    of DNA known as genes. These modifications are
    also known as genetic modifications.
    A carcinogen is a material that has the potential to
    cause cancer in people. Natural carcinogens, such
    as aflatoxin, which is formed by a fungus and
    sometimes found on stored grains, or man-made
    carcinogens, such as asbestos or cigarette smoke,
    can cause cancer. Carcinogens cause genetic
    mutations by interfering with a cell's DNA.
    Cancer information
    • One in three people in the Western world develop cancer and one in
    five die of the disease

    • There are approximately 200 types of cancer, each with different


    causes, symptoms and treatments

    • In 2007, 297,991 people were newly diagnosed with cancer in the UK


    • An individual's risk of developing cancer depends on many factors,
    including age, lifestyle and genetic make-up
    Cancer Research UK
    http://info.cancerresearchuk.org/cancerstats/incidence/?a=5441
    TYPES OF CANCER

    1. Carcinoma Epithelial cells, which cover the inside and outside


    surfaces of the body, are responsible for their formation.
    a. Adenocarcinoma is a type of cancer that develops in epithelial
    cells that contain mucus or fluids. Glandular tissues are
    epithelial tissues with this form of epithelial cell.
    Adenocarcinomas are the most common cancers of the
    breast, colon, and prostate.
    b. Basal cell carcinoma is a type of cancer that starts in the lower
    (basal) layer of the skin.
    TYPES OF CANCER

    1. Carcinoma Epithelial cells, which cover the inside and outside


    surfaces of the body, are responsible for their formation.
    c. Squamous cell carcinoma is a form of skin cancer that develops
    in squamous cells, which are epithelial cells found just beneath
    the skin's surface. Many other tissues, such as the stomach,
    intestines, lungs, bladder, and kidneys, are lined with squamous
    cells.
    TYPES OF CANCER

    1. Carcinoma Epithelial cells, which cover the inside and outside


    surfaces of the body, are responsible for their formation.
    d. Transitional cell carcinoma is a cancer that develops in the
    transitional epithelium, or urothelium, a type of epithelial tissue.
    The linings of the bladder, ureters, and part of the kidneys (renal
    pelvis), as well as a few other organs, are made up of several
    layers of epithelial cells that can get bigger or smaller. Some
    bladder, ureters, and kidney cancers are transient.
    2. Sarcoma - develops in the body's soft tissues, such as muscle,
    tendons, fat, blood vessels, lymph vessels, nerves, and joint tissue.
    3. Leukemia
    These are cancers that start in the bone marrow's blood-forming tissue.
    Strong tumors are not formed by these cancers. In the blood and bone
    marrow, large numbers of rare white blood cells (leukemia cells and
    leukemic blast cells) build up, crowding out normal blood cells. The
    body's ability to get oxygen to its tissues and maintain control can be
    hampered by a low level of normal blood cells.
    4. Lymphoma It is a type of cancer that starts in the lymphocytes
    (T cells or B cells). These are white blood cells that battle disease
    and are part of the immune system. Abnormal lymphocytes
    accumulate in lymph nodes and lymph vessels, as well as other
    tissues.
    5. Multiple Myeloma It is a cancer that starts in plasma cells,
    which are an immune cell type. Myeloma cells, which are
    irregular plasma cells, build up in the bone marrow and cause
    tumors in bones all over the body
    6. Melanoma
    Melanoma is a cancer that starts in cells that develop into
    melanocytes, specialized cells that produce melanin (the pigment
    that gives skin its color). Melanomas most often develop on the
    skin, but they may also develop in other pigmented tissues, such
    as the eye
    7. Brain and Spinal Cord Tumors

    These tumors are named for the type of cell that gave rise to
    them and the location in the central nervous system where they
    first appeared. An astrocytic tumor, for example, starts in
    astrocytes, which are star-shaped brain cells that help keep nerve
    cells healthy.
    Other Types of Tumors
    1. Germ cell tumors are cancers that start in the cells that
    produce sperm or eggs. These tumors can be benign or
    malignant and can appear almost anywhere on the body.
    2. Carcinoid tumors are slow-growing tumors that most often
    occur in the gastrointestinal tract (most often in the rectum and
    small intestine). Carcinoid tumors may spread to the liver or
    other parts of the body, secreting chemicals like serotonin and
    prostaglandins, resulting in carcinoid syndrome.
    The 20 most common causes of
    death from cancer, UK, 2008

    Cancer Research UK. Accessed July 2010


    http://info.cancerresearchuk.org/cancerstats/mortality/cancerdeaths /
    Cancer cells have altered
    genomes
    Karyotype illustrating structural abnormalities in cancer

    Credit : Mira Grigorova and Paul Edwards, Department of Pathology, University of Cambridge, unpublished
    Source: www.path.cam.ac.uk/~pawefish/BreastCellLineDescriptions/HCC38.html
    What is a mutation?

    • Germline mutation
    – A change in the DNA sequence that can be
    inherited from either parent
    • Somatic mutation
    – A change in the DNA sequence in cells other
    than sperm or egg
    – The mutation is present in the cancer cell
    and its offspring, but not in the patient’s
    healthy cells
    Mutations & cancer
    genes
    • Cancer genes are causally implicated in
    oncogenesis
    • Mutations in cancer genes can occur somatically
    or can be inherited.
    • Mutations in some cancer genes can be inherited
    from parents, in which case they are present in
    every cell of the body. Such people are at a
    higher risk of developing cancer.
    • Somatic mutations can occur in any of the cells of
    the body except the germ cells (sperm and egg)
    and therefore are not passed on to children.
    Importance of somatic DNA
    changes in human cancer
    Both
    Inherited

    Somatic

    Only 5 –10% of cancer cases have a clear hereditary component,


    e.g. BRCA1 and BRCA2 in breast cancer

    Even in those cases where susceptibility is clearly inherited, somatic


    changes are required for cancer to develop
    Cancer genes
    • There are two types of cancer genes:
    – Tumour suppressor genes
    – Oncogenes
    • To date, we know of approximately 400 somatic
    “cancer genes” * but there are almost certainly
    more to be found
    • COSMIC is a catalogue of somatic mutations
    found in cancer genes in human tumours and is
    available at:
    http://www.sanger.ac.uk/genetics/CGP/cosmic/
    *(COSMIC v47release. July 2010)
    Tumour suppressor
    gene
    These genes normally function to PREVENT
    cell growth/division

    TS

    Cancer
    Oncogene
    Genes which normally function to PROMOTE cell
    growth/division in a controlled manner

    Ras

    Cancer
    Examples of mutations
    Sequence 1 Sequence 2 Type
    ACTCGTTAGGCA ACTCCTTAGGC Substitution
    A
    ACTCGTTAGGCA ACTCGGCA Deletion

    ACTCGTTAGGCA ACTCGTTATCAGGCA Insertion

    ACTCGTTAGGCA ACTTTGCAGGCA Inversion

    ACTCGTTAGGCA ACTCGTTAGTTAGGCA Duplication


    Cancer progression
    Mutations in multiple cancer genes are required for the
    development and progression of a single cancer

    Benign Tumour

    In situ cancer

    Invasive cancer

    Metastatic
    cancer
    External causes of cancer:
    ultraviolet radiation

    www. flickr.com: lastexit


    External causes of cancer:
    tobacco smoke
    Lifestyle factor: diet
    Biological factor: virus
    • HPV is a cause of
    cervical cancer
    • Proteins from the
    virus activate and
    deactivate cancer
    genes
    • The role of HPV in
    cervical cancer has HPV in cervical epithelium
    Credit: MRC NIMR, Wellcome Images

    led to the
    development of
    vaccines
    Activity
    • The KRAS gene codes for a signalling molecule

    • Mutations in KRAS are present in many cancers,


    including pancreatic cancer

    • You have to look for the mutations by comparing


    healthy DNA sequence with tumour DNA sequence

    • Not all of you will find a mutation


    Your Worksheets
    If you find a
    mutation
    EX
    AM
    PL
    EO
    NL
    Y
    How to use the codon wheel

    Start from the centre


    and move outwards
    Mark up your sequence
    Heterozygous mutations

    Normal DNA
    sequence

    A double peak
    A indicates a mutation
    on one chromosome
    DNA change and not the other i.e.
    in cancer a heterozygous
    mutation
    T→ A

    BRAF gene mutation Nature 417, 906-7 (June 2002)


    Results
    Amino Acid Healthy DNA Tumour DNA Healthy Amino Tumour Amino
    Number
    Number Sequence
    Sequence Sequence
    Sequence Acid
    Acid Acid
    Acid
    12 GGT GTT G (glycine) V (valine)

    13 GGC GAC G (glycine) D (aspartic acid)

    30 GAC GAT D (aspartic acid) D (aspartic


    (Aspartic acid)
    acid)

    61 CAA CGA Q (glutamine) R (arginine)

    146 GCA CCA A (alanine) P (proline)

    173 GAT GAC D (aspartic


    (Aspartic acid)
    acid) D (aspartic
    (Asparticacid)
    acid)
    Significant mutations
    Amino Acid Healthy DNA Tumour DNA Healthy Amino Tumour Amino
    Number Sequence Sequence Acid Acid

    12 GGT GTT G (glycine) V (valine)

    13 GGC GAC G (glycine) D (asparatic


    acid)

    61 CAA CGA Q (glutamine) R (arginine)

    146 GCA CCA A (alanine) P (proline)


    How common?

    AA 12
    13,894

    AA 13
    2,111
    AA 61 AA 146
    212 33

    Source: COSMIC July


    2010
    RB1: tumour suppressor gene

    Source: COSMIC July


    2010
    How does this affect the
    KRAS protein?
    Amino acid 12
    Amino acid 13
    Amino acid 61
    Amino acid 146
    Amino acid 146
    What’s the impact?
    • KRAS helps to transmit external growth signals to the cell
    nucleus, driving normal cell growth. It is:
    – Activated when it binds GTP
    – Inactivated or “switched off” when GTP is hydrolysed to
    GDP

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