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Questions and Answers
What is the hallmark of cancer that involves uncontrolled cellular proliferation?
What is the hallmark of cancer that involves uncontrolled cellular proliferation?
What is a result of a mutation in a proto-oncogene?
What is a result of a mutation in a proto-oncogene?
What type of mutation can activate oncogenes?
What type of mutation can activate oncogenes?
What is the result of a cell not obeying normal signals for cell division?
What is the result of a cell not obeying normal signals for cell division?
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What is the name of the gene that encodes for a growth factor receptor?
What is the name of the gene that encodes for a growth factor receptor?
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What type of effect can increase the risk of cancer?
What type of effect can increase the risk of cancer?
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What is the result of a cell not being able to divide indefinitely?
What is the result of a cell not being able to divide indefinitely?
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What is the purpose of checkpoints in the cell cycle?
What is the purpose of checkpoints in the cell cycle?
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What is the name of the treatment for cancers that overexpress HER2/neu?
What is the name of the treatment for cancers that overexpress HER2/neu?
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What is the result of a translocation mutation leading to Burkitt Lymphoma?
What is the result of a translocation mutation leading to Burkitt Lymphoma?
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What is the primary characteristic of cancer?
What is the primary characteristic of cancer?
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What is the role of angiogenesis in tumor progression?
What is the role of angiogenesis in tumor progression?
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What is the difference between dysplasia, carcinoma in situ, and invasive cancer?
What is the difference between dysplasia, carcinoma in situ, and invasive cancer?
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What is the relationship between genetic and epigenetic alterations and cancer?
What is the relationship between genetic and epigenetic alterations and cancer?
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What is the pattern of cancer incidence and mortality in the US?
What is the pattern of cancer incidence and mortality in the US?
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What is the relationship between inheritance and cancer?
What is the relationship between inheritance and cancer?
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What is the term for the study of the structure and function of cells and tissues in cancer?
What is the term for the study of the structure and function of cells and tissues in cancer?
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What is the role of environment, heredity, and behavior in cancer development?
What is the role of environment, heredity, and behavior in cancer development?
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What is the characteristic of malignant tumors that distinguishes them from benign tumors?
What is the characteristic of malignant tumors that distinguishes them from benign tumors?
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What is the term for the study of the functions and interactions of all the genes in the genome?
What is the term for the study of the functions and interactions of all the genes in the genome?
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What is the term for a premalignant condition characterized by increased cell growth and cellular atypia?
What is the term for a premalignant condition characterized by increased cell growth and cellular atypia?
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What type of cancer arises from epithelial tissues?
What type of cancer arises from epithelial tissues?
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What is the term for a preinvasive epithelial tumor of glandular or squamous cell origin?
What is the term for a preinvasive epithelial tumor of glandular or squamous cell origin?
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What is the term for the genetic changes that occur in somatic cells and are not inherited?
What is the term for the genetic changes that occur in somatic cells and are not inherited?
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What is the term for a cancer that is caused by a strong cancer gene inherited through a germ cell line?
What is the term for a cancer that is caused by a strong cancer gene inherited through a germ cell line?
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What is the term for the study of the interactions between genes and environmental factors that lead to disease?
What is the term for the study of the interactions between genes and environmental factors that lead to disease?
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What is the term for a biopsy of the cervix that involves removing a chunk of tissue?
What is the term for a biopsy of the cervix that involves removing a chunk of tissue?
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What is the term for the progression of dysplasia to carcinoma in situ?
What is the term for the progression of dysplasia to carcinoma in situ?
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What is the main challenge in treating cancer?
What is the main challenge in treating cancer?
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What is the primary purpose of surgery in cancer treatment?
What is the primary purpose of surgery in cancer treatment?
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Which type of cancer is well-suited for radiation therapy?
Which type of cancer is well-suited for radiation therapy?
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What is the goal of targeted cancer therapy?
What is the goal of targeted cancer therapy?
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What is the result of the T(9;22) translocation in chronic myeloid leukemia?
What is the result of the T(9;22) translocation in chronic myeloid leukemia?
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What is the primary mechanism of chemotherapy agents?
What is the primary mechanism of chemotherapy agents?
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What is the function of the Rb protein in normal cells?
What is the function of the Rb protein in normal cells?
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What is the definition of a benign tumor?
What is the definition of a benign tumor?
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What is the function of the p53 protein in normal cells?
What is the function of the p53 protein in normal cells?
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What is the minimum number of mutations required to inactivate a tumor suppressor gene?
What is the minimum number of mutations required to inactivate a tumor suppressor gene?
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What is the purpose of immunotherapy in cancer treatment?
What is the purpose of immunotherapy in cancer treatment?
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What is the classification of cancer based on?
What is the classification of cancer based on?
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What is the characteristic of cancer cells that leads to tumor growth and metastasis?
What is the characteristic of cancer cells that leads to tumor growth and metastasis?
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What is the characteristic of malignant tumors?
What is the characteristic of malignant tumors?
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What is the result of the inactivation of tumor suppressor genes in cancer cells?
What is the result of the inactivation of tumor suppressor genes in cancer cells?
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What is the main difference between benign and malignant tumors?
What is the main difference between benign and malignant tumors?
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What is the function of Imatinib in the treatment of chronic myeloid leukemia?
What is the function of Imatinib in the treatment of chronic myeloid leukemia?
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What is the hallmark of cancer characterized by the formation of new blood vessels?
What is the hallmark of cancer characterized by the formation of new blood vessels?
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What is the characteristic of familial cancer syndromes?
What is the characteristic of familial cancer syndromes?
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What is the result of the Philadelphia chromosome in chronic myeloid leukemia?
What is the result of the Philadelphia chromosome in chronic myeloid leukemia?
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What is the role of angiogenic factors and angiogenic inhibitors in wound healing?
What is the role of angiogenic factors and angiogenic inhibitors in wound healing?
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Why is access to blood supply important for the growth and spread of cancer?
Why is access to blood supply important for the growth and spread of cancer?
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What is the role of HIF-1α in cancer?
What is the role of HIF-1α in cancer?
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What is the effect of inactivating tumor suppressor genes or increasing oncogenes in cancer?
What is the effect of inactivating tumor suppressor genes or increasing oncogenes in cancer?
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What is the effect of increased HIF-1α on cancer?
What is the effect of increased HIF-1α on cancer?
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What is the function of angiogenesis inhibitors in normal tissue?
What is the function of angiogenesis inhibitors in normal tissue?
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Why are vessels formed within tumors different from those in healthy tissue?
Why are vessels formed within tumors different from those in healthy tissue?
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What is the function of apoptosis in cells?
What is the function of apoptosis in cells?
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What is the role of p53 in apoptosis?
What is the role of p53 in apoptosis?
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What is the use of tumor markers?
What is the use of tumor markers?
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What is the characteristic of familial cancers?
What is the characteristic of familial cancers?
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How do we determine if a cancer is hereditary?
How do we determine if a cancer is hereditary?
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What is the significance of a family pedigree in determining hereditary cancer?
What is the significance of a family pedigree in determining hereditary cancer?
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What is the characteristics of an autosomal dominant disorder?
What is the characteristics of an autosomal dominant disorder?
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What is the percentage of breast cancer cases that are inherited in the US?
What is the percentage of breast cancer cases that are inherited in the US?
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What is the function of the BRCA1 and BRCA2 genes?
What is the function of the BRCA1 and BRCA2 genes?
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What is the lifetime risk of developing breast cancer for women with a BRCA1 or BRCA2 mutation?
What is the lifetime risk of developing breast cancer for women with a BRCA1 or BRCA2 mutation?
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What is the risk of colorectal cancer in people with one affected first-degree relative?
What is the risk of colorectal cancer in people with one affected first-degree relative?
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What is the function of the APC gene in Familial Adenomatous Polyposis (FAP)?
What is the function of the APC gene in Familial Adenomatous Polyposis (FAP)?
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What is the lifetime risk of colorectal cancer in individuals with Hereditary Nonpolyposis Colorectal Cancer (HNPCC)?
What is the lifetime risk of colorectal cancer in individuals with Hereditary Nonpolyposis Colorectal Cancer (HNPCC)?
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What is the consequence of DNA repair being affected?
What is the consequence of DNA repair being affected?
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What is the purpose of Genetic Counseling?
What is the purpose of Genetic Counseling?
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Who may be suggested for Predictive Genetic Testing?
Who may be suggested for Predictive Genetic Testing?
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What is Hereditary Nonpolyposis Colorectal Cancer (HNPCC) associated with?
What is Hereditary Nonpolyposis Colorectal Cancer (HNPCC) associated with?
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What criteria are used to identify patients with HNPCC mutations?
What criteria are used to identify patients with HNPCC mutations?
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Study Notes
Biology of Cancer
- Cancer is a disease caused by uncontrolled division of abnormal cells in a part of the body.
- It is a collection of more than 100 different diseases, each caused by a specific and often unique age-related accumulation of genetic and epigenetic alterations.
- Environment, heredity, and behavior interact to modify the risk of developing cancer and the response to treatment.
Hallmarks of Cancer
- There are 8 hallmarks and 2 traits that enable cancer progression.
- The hallmarks of cancer include:
- Sustaining proliferative signaling
- Evading growth suppressors
- Resisting cell death
- Inducing angiogenesis
- Activating invasion and metastasis
- Tumor-promoting inflammation
- Enabling replicative immortality
- Deregulating cellular energetics
- Genomic instability and mutation
- Avoiding immune destruction
Cell Cycle and Cell Division
- Checkpoints are found at G1, S, and M (in Metaphase of M) phases of the cell cycle.
- G1 checkpoint: cell checks for DNA damage and resources availability.
- S checkpoint: cell checks for DNA errors.
- M checkpoint: cell checks for sister chromatid attachment to mitotic spindles.
- Proto-oncogenes: normally ensure that checkpoints are followed.
- Mutated proto-oncogenes are called oncogenes, which can cause checkpoint dysfunction.
Oncogenes and Tumor-Suppressor Genes
- Oncogenes: genes that encode components of pathways that regulate normal cell proliferation.
- Her2/neu: a gene that encodes for a growth factor receptor, often overexpressed in breast cancer.
- Tumor-suppressor genes: genes that regulate the cell cycle and inhibit proliferation.
- Examples of tumor-suppressor genes: Rb, p53, BRCA1.
- Rb: contributes to the control of cell division, regulates antigrowth signals.
- p53: detects genomic damage, halts the cell cycle, and initiates DNA repair.
Inheritance and Cancer
- Inactivation of tumor-suppressor genes requires at least two mutations (one in each allele).
- A single mutation in the germline cells (sperm or egg) results in the transmission of cancer-causing genes from one generation to the next.
- Familial cancer syndromes: caused by loss of tumor-suppressor gene function, examples include Retinoblastoma, Li-Fraumeni syndrome, and Familial melanoma.
Angiogenesis
- Angiogenesis: the process of establishing new blood vessels.
- Hypoxia-inducible factor 1alpha (HIF-1⍺): a major regulator of angiogenesis in normal tissue.
- In cancer, HIF-1⍺ is increased, leading to increased angiogenic factors and vascularization.
Apoptosis
- Apoptosis: programmed cell death.
- Intrinsic pathway: monitors for abnormal physiology (cellular stress) and triggers apoptosis.
- Extrinsic pathway: relatively dormant until the death receptor is activated.
- In cancer, p53 suppression messes up the intrinsic pathway for apoptosis.
Cancer Treatments
- Surgery: allows for tissue diagnosis and staging, often definitive treatment for localized cancers.
- Radiation therapy: used to kill cancer cells, produces slow changes in most cancers.
- Chemotherapy: attacks rapidly dividing cells, often given in combinations to limit toxicity.
- Immunotherapy: targets unique antigens on cancer cells, aims to induce an immune response.
Tissue Pathology of Cancer
- Neoplasm/Tumor: formation or presence of a new, abnormal growth of tissue.
- Malignant: a tumor tending to invade normal tissue or recur after removal.
- Benign: a slow-growing tumor that is non-invasive and does not metastasize.
- Cancer: a malignant tumor.
Cancer Classification
- Based on: tissue and organ of origin, extent of distribution (stages), microscopic appearance of the malignant tumor, and critical genetic changes in the cancer cells.
- Benign tumors: usually encapsulated, well-demarcated, and do not invade beyond their capsule.
- Malignant tumors: characterized by rapid cell growth, loss of differentiation, and absence of normal tissue organization.
Progression to Malignancy
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Cancers develop incrementally as they accumulate genetic mutations.
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Dysplasia: a premalignant condition, can range from mild to severe.
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Carcinoma In Situ (CIS): preinvasive epithelial tumors of glandular or squamous cell origin.
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Invasive carcinoma: histologic features of malignancy that invade past the basement membrane.### Genomics and Cancer
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Genomics involves the study of germ cell mutations and somatic cell mutations, as well as the interactions between genes, environment, and viral or bacterial genes.
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Cancer is driven by genetic alterations and changes in epigenetic regulation.
Types of Cancer
- Sporadic Cancers: involve genetic changes in somatic cells, are the majority of cancer cases, occur at older ages (60s, 70s, 80s), and have no family history.
- Hereditary Cancers: involve a strong cancer gene inherited through a germ cell line, have high risks to other family members and usually risks for other types of cancer too.
- Familial Cancers: involve multiple family members with the same cancer, with an unknown cause, and share similar genes and lifestyle, environment, and exposures.
Identifying Hereditary Cancers
- Family history and pedigree are used to identify hereditary cancers.
- Genetic counseling and testing are also used to determine hereditary cancer risks.
- "Clues" for hereditary cancers include: young ages of diagnosis, multiple family members with cancer, multiple generations with cancer, multiple cancers in the same person, and related cancers.
Family Pedigree
- A family pedigree allows for a larger picture of the family's cancer history.
- It helps to narrow down which gene to test for and whom to consider testing.
- It also helps with test interpretation.
Interpreting a Pedigree Chart
- Remember the Mendelian modes of inheritance.
- Determine if the pedigree chart shows an autosomal or X-linked disease.
- Determine whether the disorder is dominant or recessive.
Breast Cancer
- Breast cancer is the most common cancer in women, affecting ~12% of American women who live to 85 years or older.
- 5-10% of breast cancer cases in the US are inherited.
- BRCA1 and BRCA2 are autosomal dominant mutations that increase the risk of breast cancer.
Hereditary Breast Cancer
- Women with BRCA1 or BRCA2 mutations have a 50-80% lifetime risk of developing breast cancer.
- BRCA1 also increases the risk of ovarian cancer and moderate risk of colon and prostate cancer.
- BRCA2 increases the risk of ovarian cancer.
BRCA1 and BRCA2
- Both genes are tumor suppressor genes that code for proteins important in DNA damage repair.
- Both genes "put the brakes" on DNA replication until DNA repair is completed.
- With a BRCA1 or BRCA2 mutation, one of the "sets of brakes" is broken, leading to impaired DNA repair.
Colorectal Cancer
- ~1 in 21 Americans will develop colorectal cancer.
- Family history increases the risk of colorectal cancer.
- Hereditary syndromes that increase the risk of colorectal cancer include Familial Adenomatous Polyposis (FAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or Lynch syndrome.
Hereditary Colorectal Cancer Syndromes
- Familial Adenomatous Polyposis (FAP): caused by a mutation in the APC gene, which encodes a tumor suppressor.
- Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or Lynch syndrome: caused by mutations in genes involved in DNA repair, with an 80% lifetime risk of colorectal cancer.
Cancer Risks and Genetic Testing
- When DNA repair is affected, cancer-causing mutations can persist in cells, leading to tumor growth.
Autosomal Dominant Inheritance
- Increases risk of colon cancer (80%), endometrial cancer (60%), ovarian, stomach, small intestine, biliary tract, renal, and skin cancers.
Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
- Identified using Bethesda and Amsterdam Criteria.
Genetic Testing for Cancer Risk
- Predictive Genetic Testing looks for inherited gene mutations that increase the risk of certain cancers.
- Suggested for:
- Individuals with a strong family history of certain cancers.
- Those already diagnosed with cancer.
- Family members of individuals with an inherited gene mutation.
Genetic Counseling
- A genetic counselor evaluates family history and creates a family pedigree.
- Counsels patients on risk of inherited cancer and management if at high risk.
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Description
Learn about the definition, causes, and characteristics of cancer, including the hallmarks and traits that enable its progression.