Shared Flashcard Set

Details

Medical Pathology and Genetics
PPT8: Cancer Pathology and Genetics
74
Pathology
Graduate
02/11/2012

Additional Pathology Flashcards

 


 

Cards

Term
The development of cancer (oncogenesis) results from mutations in a vast array of genes that regulate what two things?
Definition
-cellular proliferation
-programmed cell death
Term
When cancer occurs as part of a hereditary cancer syndrome, from where does the initial cancer-causing mutation come?
Definition
it is inherited through the germline
Term
Most cancers are sporadic bc the mutations occur in a single ______ cell, which then divides and proceeds to develop into the cancer
Definition
somatic
Term
What percentage of cancers are hereditary?
Definition
5%
Term
What percentage of cancers are sporadic?
Definition
95%
Term
Cancer cells are clonal descendants from one ______ cell
Definition
mutant
Term
What is the primary risk factor for cancer? why?
Definition
age, bc the cell accumulates a number of specific mutations over a long period of time
Term
What is neoplasia? Of what does it lead to the growth?
Definition
Neoplasia is a disease process characterized by uncontrolled cellular proliferation leading to the growth of a tumor (neoplasm)
Term
What is a benign tumor?
Definition
One that remains in its site of origin and does not invade other tissues
Term
For a tumor to be cancer what must it also be?
Definition
malignant, which means it is capable of metastasizing to other locations
Term
What is metastasis?
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
Term
Benign tumors are usually designated by adding _______to cell type of origin
Definition
-oma
-ex's: adenoma, leiomyoma, chrondroma
Term
What is a carcinoma?
Definition
a malignant tumor that arises in epithelial tissue
-adenocarcinoma
-squamos cell carcinoma
Term
What is a sarcoma?
Definition
a malignant tumor that arises in mesenchymal tissue
-Ex's: chondrosarcoma, angiosarcoma, rhabdomyosarcoma
Term
What is a leukemia?
Definition
a malignant tumor arising from hematopoietic cells
Term
what is a lymphoma?
Definition
a malignant tumor arising in lymphoid tissue
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?
Definition
-Proto-oncogenes
-Tumor supressor genes (TSG's)
Term
what is the normal function of proto-oncogenes? What type of mutation in these cause cancer?
Definition
normally turn on or increase the rate of cell division

-DOMINANT mutations in proto-oncogenes cause cancer
Term
What is the normal function of a TSG? what type of mutation causes cancer in these genes?
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
Term
Genes that increase or decrease the rate of cell division regulate the __/__ and __/__ checkpoints of the cell cycle
Definition
G1/S and G2/M
Term
In oncogenesis, a single cell acquires mutations in genes that permit the cell to grow out of control and evade ______/___/______
Definition
programmed cell death
Term
What is an oncogene? how many have been identified?
Definition
-a mutant proto-oncogene
-induce or continue uncontrolled cell proliferation
-more than 50
Term
Oncogenes are permanently "switched on" proto-oncogenes that cause uncontrolled cell division. What three things can the mutations produce/cause?
Definition
-produce an altered gene product
-overproduce a normal gene product
-increase the number of copies of a normal gene
Term
What is the normal function of the ras proto-oncogene when active and inactive?
Definition
-active: transfers molecular signals from the plasma membrane to the cell nucleus and initiates cell division
-inactive: cell division is inhibited
Term
What happens to a ras proto-oncogene when it is mutated and becomes an oncogene?
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
Term
Some cancers, such as CML, are caused by ________ events, creating hybrid genes that activate cell division
Definition
translocation
Term
Expression of a philadelphia chromosome (t; 9:22) in a patient with CML, leads to what?
Definition
Ph1 contains a hybrid BCR/C-ABL gene that causes unregulated cell growth and CML
Term
Deletion or inactivation of TSGs cause what?
Definition
cells to divide continuously
Term
What are 3 functions of the gatekeepers TSGs?
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
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?
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
Term
TSG mutations arising from sporadic cancers begin with a patient who inherits what type of alleles? How is cancer initiated?
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
Term
a retinoblastoma is a mutation of a _______
Definition
TSG
Term
Why does retinoblastoma usually occur in children?
Definition
because mature mature retinal cells do not transform into tumors
Term
A mutation in what gene on what chromosome causes retinoblastoma?
Definition
mutations in the RB1 gene on chromosome 13
Term
Describe familial retinoblastoma (hereditary)
-what genes are inherited?
-what is the chance of developing the disease?
-how many eyes does it usually involve
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
Term
Explain sporadic retinoblastoma
Definition
-mutations of both copies of RB1 gene occur in a single cell
-usually involves one eye and occurs later in life
Term
The RB1 gene encodes what tumor suppressor protein?
Definition
the pRB protein, which controls the G1/S transition in the cell cycle
-without pRB cell division is uncontrolled
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?
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
Term
All patients with bilateral disease have ______/____/______ but not all patients with that type of mutation develop bilateral disease
Definition
germline RB1 mutation
Term
Retinoblastoma is diagnosed before 5 yoa in what percentage of patients? Is it fatal if left untreated?
Definition
80-95%
yes it is fatal if untreated
Term
Patients with germline RB1 mutations have a markedly ______ risk of secondary neoplasms
Definition
increased
Term
What are the goals of therapy for a retinoblastoma?
Definition
cure the dx and preserve as much vision as possible
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?
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.
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?
Definition
45%
7-15% (reflects the relative proportion of germ line mutation vs. somatic mutations in pt's with unilateral dx)
Term
Nearly ___% of retinoblastomas are the first individuals affected in within the family.
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).
Term
What is TP53? what is it usually referred to as?
Definition
a tumor suppressor gene that monitors cellular stress (usually referred to as just p53)
Term
What activates TP53?
Definition
anoxia, inappropriate oncogene signaling, or DNA damage
Term
TP53 prevents neoplastic transformation by several mechanisms, what are 3 of them?
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)
Term
___% of tumors are involved with homozygous loss of TP53
Definition
70%
Term
Cyclin D and CDK4 (cyclin dependent kinase) are ________ in many cancers. What type of gene are they?
Definition
over expressed
oncogenes
Term
CDKIs are ________ in many cancers. What type of genes are they?
Definition
inactivated
TSGs
Term
Caretaker TSGs help maintain the integrity of the genome. What three things do they encode for?
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
Term
What does loss-of-function of caretaker genes permit?
Definition
-mutations to accumulate in oncogenes and gatekeeper genes, which, in concert go on to initiate and promote cancer
Term
What is another name for hereditary nonpolyposis colon cancer?
Definition
Lynch syndrome
Term
what is lynch syndrome?
Definition
a form of colon cancer that develops with very few polyps, but each with a high probability of becoming cancerous
Term
Lynch syndrome is caused by what type of mutation in what type of gene?
Definition
an autosomal dominant trait caused by mutations in DNA mismatch repair genes: MLH1, MSH2, MHS6, or PMS2
Term
_____ alleles of the DNA mismatch repair gene must be __________for cancer to develop
Definition
both
inactivated
Term
What do proteins encoded by DNA mismatch repair genes do?
Definition
Fix errors made during DNA replication
Term
What happens when mismatch repair genes are inactivated by mutation, two things are likely to happen?
Definition
-DNA mutations can accumulate in proto-oncogenes and other TSGs
-DNA mutations accumulate in microsatellites, promoting microsatellite instability (MSA) and overall genomic instability
Term
If a pt presents with colorectal CA what do they need to be screened for?
Definition
lynch syndrome
Term
miRNAs function as ______ regulators of gene expression
Definition
negative
Term
What happens when there is loss of miRNA's that down regulate proto-oncogenes?
Definition
leads to over expression of the pro to-oncogene
Term
What happens what miRNAs that down regulate TSGs are activated?
Definition
suppression of TSG expression
Term
Tumors are initiated by different types of genetic alterations, name 4.
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
Term
What types of changes are hallmark of cancer, particularly in later and more malignant invasive stages of tumor development?
Definition
cytogenetic changes
Term
What three types of cytogenetic changes are commonly seen?
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
Term
DNA damage from UV light often causes what?
Definition
thymine dimer
-chemical bonds form between a pair of adjacent thymine bases in a DNA molecule
-distorts DNA molecule and affects replication
Term
What is xeroderma pigmentosum?
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
Term
What type of cancer does the epstein-barr virus cause?
Definition
burkitt's lymhphoma
Term
what type of cancer does the hep c and b viruses cause?
Definition
hepatocellular carcinoma
Term
which strains of HPV cause 70% of cervical cancers?
Definition
16 and 18
Term
social behavior contributes to approx ---% of all cancers in the US
Definition
50%
Term
What is grading of cancer?
Definition
what a pathologist does.
-cytological evaluation
Term
what is staging of cancer?
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
Supporting users have an ad free experience!