Term
| The development of cancer (oncogenesis) results from mutations in a vast array of genes that regulate what two things? |
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Definition
-cellular proliferation
-programmed cell death |
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Term
| When cancer occurs as part of a hereditary cancer syndrome, from where does the initial cancer-causing mutation come? |
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Definition
| it is inherited through the germline |
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Term
| Most cancers are sporadic bc the mutations occur in a single ______ cell, which then divides and proceeds to develop into the cancer |
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Definition
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Term
| What percentage of cancers are hereditary? |
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Definition
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Term
| What percentage of cancers are sporadic? |
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Definition
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Term
| Cancer cells are clonal descendants from one ______ cell |
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Definition
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Term
| What is the primary risk factor for cancer? why? |
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Definition
| age, bc the cell accumulates a number of specific mutations over a long period of time |
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Term
| What is neoplasia? Of what does it lead to the growth? |
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Definition
| Neoplasia is a disease process characterized by uncontrolled cellular proliferation leading to the growth of a tumor (neoplasm) |
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Term
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Definition
| One that remains in its site of origin and does not invade other tissues |
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Term
| For a tumor to be cancer what must it also be? |
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Definition
| malignant, which means it is capable of metastasizing to other locations |
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Term
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Definition
A process by which cells detach from the primary tumor and move to other sites in the body, forming new malignant tumors
-the ability to invade new tissues results from new mutations in cancer cells |
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Term
| Benign tumors are usually designated by adding _______to cell type of origin |
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Definition
-oma
-ex's: adenoma, leiomyoma, chrondroma |
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Term
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Definition
a malignant tumor that arises in epithelial tissue
-adenocarcinoma
-squamos cell carcinoma |
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Term
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Definition
a malignant tumor that arises in mesenchymal tissue
-Ex's: chondrosarcoma, angiosarcoma, rhabdomyosarcoma |
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Term
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Definition
| a malignant tumor arising from hematopoietic cells |
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Term
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Definition
| a malignant tumor arising in lymphoid tissue |
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Term
| Study of two classes of genes has established a relationship between cancer, regulation of cell growth and division, and the cell cycle. What are these two classes of genes? |
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Definition
-Proto-oncogenes
-Tumor supressor genes (TSG's) |
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Term
| what is the normal function of proto-oncogenes? What type of mutation in these cause cancer? |
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Definition
normally turn on or increase the rate of cell division
-DOMINANT mutations in proto-oncogenes cause cancer |
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Term
| What is the normal function of a TSG? what type of mutation causes cancer in these genes? |
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Definition
-normally turn off or decrease the rate of cell division
-Gatekeepers (there are several points of the cell cycle where they stop progression past that point)
-Caretakers (of the whole genome, usually involved in DNA repair etc. mutations will develop if they do not regulate)
-RECESSIVE mutation in tumor supressor genes cause cancer |
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Term
| Genes that increase or decrease the rate of cell division regulate the __/__ and __/__ checkpoints of the cell cycle |
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Definition
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Term
| In oncogenesis, a single cell acquires mutations in genes that permit the cell to grow out of control and evade ______/___/______ |
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Definition
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Term
| What is an oncogene? how many have been identified? |
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Definition
-a mutant proto-oncogene
-induce or continue uncontrolled cell proliferation
-more than 50 |
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Term
| Oncogenes are permanently "switched on" proto-oncogenes that cause uncontrolled cell division. What three things can the mutations produce/cause? |
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Definition
-produce an altered gene product
-overproduce a normal gene product
-increase the number of copies of a normal gene |
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Term
| What is the normal function of the ras proto-oncogene when active and inactive? |
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Definition
-active: transfers molecular signals from the plasma membrane to the cell nucleus and initiates cell division
-inactive: cell division is inhibited |
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Term
| What happens to a ras proto-oncogene when it is mutated and becomes an oncogene? |
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Definition
| the oncogene does not need to receive a growth factor signal, it is "on" all the time, telling the cell to divide all the time |
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Term
| Some cancers, such as CML, are caused by ________ events, creating hybrid genes that activate cell division |
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Definition
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Term
| Expression of a philadelphia chromosome (t; 9:22) in a patient with CML, leads to what? |
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Definition
| Ph1 contains a hybrid BCR/C-ABL gene that causes unregulated cell growth and CML |
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Term
| Deletion or inactivation of TSGs cause what? |
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Definition
| cells to divide continuously |
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Term
| What are 3 functions of the gatekeepers TSGs? |
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Definition
-regulate cell growth and passage through the cell cycle
-mediate programmed cell death
-loss-of-function mutations of gatekeepers genes lead to uncontrolled cell accumulation |
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Term
| TSG mutations occurs in both hereditary and sporadic forms. Explain how the hereditary (familial) cancers come about: what types of alleles are inherited? how is the cancer actually initiated? |
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Definition
-inherit on inactive allele and one normal allele
-all cells are heterozygous for the germ line mutation
-cancer is initiated when a second inactivating mutation occurs in the normal TSG allele in one cell of the body |
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Term
| TSG mutations arising from sporadic cancers begin with a patient who inherits what type of alleles? How is cancer initiated? |
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Definition
-two normal alleles
-all cells are homozygous for the normal allele
-cancer is initiated when both normal alleles are inactivated by two somatic events in the same cell |
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Term
| a retinoblastoma is a mutation of a _______ |
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Definition
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Term
| Why does retinoblastoma usually occur in children? |
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Definition
| because mature mature retinal cells do not transform into tumors |
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Term
| A mutation in what gene on what chromosome causes retinoblastoma? |
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Definition
| mutations in the RB1 gene on chromosome 13 |
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Term
Describe familial retinoblastoma (hereditary)
-what genes are inherited?
-what is the chance of developing the disease?
-how many eyes does it usually involve |
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Definition
-individuals inherit one mutant copy of RB1 gene and one normal copy of the RB1 gene
-normal copy of RB1 gene acquires a spontaneous mutation
-85% to 95% chance of developing the disease
-usually involves both eyes and occurs earlier in life |
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Term
| Explain sporadic retinoblastoma |
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Definition
-mutations of both copies of RB1 gene occur in a single cell
-usually involves one eye and occurs later in life |
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Term
| The RB1 gene encodes what tumor suppressor protein? |
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Definition
the pRB protein, which controls the G1/S transition in the cell cycle
-without pRB cell division is uncontrolled |
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Term
| An RB1 germline mutation is found in ____% of patients with retinoblastoma, but only ____% of all patients have a hx of other affected family member. How is this so? |
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Definition
40
10
-the sperm that fertilized the egg contained the mutant gene. Mutation occurred during spermatogenesis and therefore dad doesn't have it in all the cells in his body |
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Term
| All patients with bilateral disease have ______/____/______ but not all patients with that type of mutation develop bilateral disease |
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Definition
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Term
| Retinoblastoma is diagnosed before 5 yoa in what percentage of patients? Is it fatal if left untreated? |
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Definition
80-95%
yes it is fatal if untreated |
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Term
| Patients with germline RB1 mutations have a markedly ______ risk of secondary neoplasms |
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Definition
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Term
| What are the goals of therapy for a retinoblastoma? |
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Definition
| cure the dx and preserve as much vision as possible |
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Term
| If retinoblastoma is unilateral at the time of the pt's presentation, the pt needs frequent examinations to detect any new retinoblastomas in the unaffected eye, why? |
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Definition
| -30% of apparently sporadic cases are caused by the inheritance of a new germline mutation. Meaning neither parents are carriers, dad's sperm was mutated. |
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Term
If a parent had bilateral retinoblastoma, what is the risk of an affected child?
If a parent had unilateral retinoblastoma, what is the risk of an affected child? |
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Definition
45%
7-15% (reflects the relative proportion of germ line mutation vs. somatic mutations in pt's with unilateral dx) |
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Term
| Nearly ___% of retinoblastomas are the first individuals affected in within the family. |
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Definition
90
(a germline mutation is found in 40% of patients with retinoblastoma, but only 10% of all patients have a history of other affected family members). |
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Term
| What is TP53? what is it usually referred to as? |
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Definition
| a tumor suppressor gene that monitors cellular stress (usually referred to as just p53) |
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Term
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Definition
| anoxia, inappropriate oncogene signaling, or DNA damage |
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Term
| TP53 prevents neoplastic transformation by several mechanisms, what are 3 of them? |
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Definition
-activation of temporary cell cycle arrest (quiescence), and induction of DNA repair genes
-induction of permanent cell cycle arrest (senescence)
-induction of programmed cell death (apoptosis) |
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Term
| ___% of tumors are involved with homozygous loss of TP53 |
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Definition
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Term
| Cyclin D and CDK4 (cyclin dependent kinase) are ________ in many cancers. What type of gene are they? |
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Definition
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Term
| CDKIs are ________ in many cancers. What type of genes are they? |
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Definition
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Term
| Caretaker TSGs help maintain the integrity of the genome. What three things do they encode for? |
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Definition
-proteins responsible for detecting and repairing mutations (DNA repair genes)
-proteins involved in normal chromosome disjunction during mitosis
-components of programmed cell death machinery |
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Term
| What does loss-of-function of caretaker genes permit? |
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Definition
| -mutations to accumulate in oncogenes and gatekeeper genes, which, in concert go on to initiate and promote cancer |
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Term
| What is another name for hereditary nonpolyposis colon cancer? |
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Definition
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Term
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Definition
| a form of colon cancer that develops with very few polyps, but each with a high probability of becoming cancerous |
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Term
| Lynch syndrome is caused by what type of mutation in what type of gene? |
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Definition
| an autosomal dominant trait caused by mutations in DNA mismatch repair genes: MLH1, MSH2, MHS6, or PMS2 |
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Term
| _____ alleles of the DNA mismatch repair gene must be __________for cancer to develop |
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Definition
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Term
| What do proteins encoded by DNA mismatch repair genes do? |
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Definition
| Fix errors made during DNA replication |
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Term
| What happens when mismatch repair genes are inactivated by mutation, two things are likely to happen? |
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Definition
-DNA mutations can accumulate in proto-oncogenes and other TSGs
-DNA mutations accumulate in microsatellites, promoting microsatellite instability (MSA) and overall genomic instability |
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Term
| If a pt presents with colorectal CA what do they need to be screened for? |
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Definition
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Term
| miRNAs function as ______ regulators of gene expression |
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Definition
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Term
| What happens when there is loss of miRNA's that down regulate proto-oncogenes? |
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Definition
| leads to over expression of the pro to-oncogene |
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Term
| What happens what miRNAs that down regulate TSGs are activated? |
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Definition
| suppression of TSG expression |
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Term
| Tumors are initiated by different types of genetic alterations, name 4. |
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Definition
-gain of function mutations that turn one allele for a pro to-oncogene into an oncogene
-ectopic and heterochronic mutations of proto-oncogenes
-chromosome translocations
-loss of function of both alleles, or a dominant negative mutation of one allele, of TSGs |
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Term
| What types of changes are hallmark of cancer, particularly in later and more malignant invasive stages of tumor development? |
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Definition
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Term
| What three types of cytogenetic changes are commonly seen? |
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Definition
-aneuploidy and aneusomy: deletion or duplication of entire chromosomes, or segments
-gene amplification: segments of chromosomes are replicated multiple times
-chromosomal translocations: the exchange of segments between chromosomes |
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Term
| DNA damage from UV light often causes what? |
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Definition
thymine dimer
-chemical bonds form between a pair of adjacent thymine bases in a DNA molecule
-distorts DNA molecule and affects replication |
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Term
| What is xeroderma pigmentosum? |
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Definition
-an autosomal recessive mutation in one of eight different DNA repair genes
-extremely sensitive to UV exposure from sun
-skin cancer from sun is 1000x greater than normal |
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Term
| What type of cancer does the epstein-barr virus cause? |
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Definition
|
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Term
| what type of cancer does the hep c and b viruses cause? |
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Definition
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Term
| which strains of HPV cause 70% of cervical cancers? |
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Definition
|
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Term
| social behavior contributes to approx ---% of all cancers in the US |
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Definition
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Term
| What is grading of cancer? |
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Definition
what a pathologist does.
-cytological evaluation |
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Term
| what is staging of cancer? |
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Definition
-size of primary lesions and extent of metastases
-clinical evaluation of pt (imaging and surgery
-TNM (size (1234), lymph node (0123), metastasis (01)
**GREATER CLINICAL VALUE THAN GRADING |
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