Cancer Genetics I - IN (lecture 15)

Question 1

T/F - tumors are clonal

Answer 1

True - they start as a single cell with a mutation which proliferates to form a group of similarly abnormal cells

Question 2

define malignancy

Answer 2

uncontrolled cell growth characterized by a change in the normal organization pattern of tissues or cells

Question 3

define metastasis

Answer 3

when cells become invasive OR pick up and bounce to another site, while retaining their original cell morphology

Question 4

define cancer

Answer 4

malignant tumor of potentially unlimited overgrowth hat expands locally by invasion and systematically by metastasis

Question 5

what type of tissue does sarcoma imply

Answer 5

mesenchymal - bone, cartilage, muscle, fat

Question 6

what type of tissue does carcinoma imply

Answer 6

epitheloid tissue

Question 7

what are the hallmarks of cancer

Answer 7

mutation or loss of genes involved in cell control, growth, division, proliferation, metabolism
chromosome instability

Question 8

what is an oncogene

Answer 8

dominantly acting gene involved in unregulated cell growth and proliferation - can be carried by viruses - there are very few true oncogenes known in humans, instead we have proto-oncogenes

Question 9

what is a proto-oncogene

Answer 9

critical housekeeping genes, mutation can result in “activation” which, after a gain of function mutation, can lead to tumorigenesis
dominant - only one mutation required

Question 10

How does Chronic Myelogenous Leukemia work

Answer 10

CML is a translocation between chromosomes 9 and 22, resulting in a chimeric protein, loss of regulatory control and overproduction of tyrosine kinase, a cell regulator protein

Question 11

How does Acute Promyelocytic Leukemia work

Answer 11

proto-oncogene activation, characterized by a diagnostic 15;17 translocation breaking in the PML gene on chromosome 15 and the RARA gene on chrom 17, giving rise to a chimeric protein

Question 12

What is a tumor suppressor

Answer 12

genetic element whose loss or inactivation allows the cell to display an alternate phenotype leading to neoplastic growth - the oncogenic potential arises when the gene activity is lost - these genes are RECESSIVE AS FUCK

Question 13

how many alleles need to mutate in order for tumorigenesis to occur in proto-oncogenes? tumor suppressors?

Answer 13

proto-oncogenes - ONE

tumor suppressors - DOS

Question 14

what is a gate-keeper

Answer 14

genes that suppress tumors by regulating cell cycle or overgrowth inhibition

Question 15

what is a care-taker

Answer 15

the normal function of a caretaker gene is to maintain cellular integrity, usually by repairing DNA damage

Question 16

What are RB1 and p53?

Answer 16

RB1 - first tumor suppressor known

p53 - on short arm of C17, the most ubiquitous suppressor

Question 17

How does RB1 work?

Answer 17

functions in regulation of cell cycle by controlling progression from G1 to S - loss of function eliminates a checkpoint in mitosis causing uncontrolled growth

Question 18

What is Knudson’s Two Hit Hypothesis?

Answer 18

two mutations in same cell, sporadic = unilateral, inherited = bilateral, appears dominant, but tumor suppressors are recessive, so the pedigree is deceptive

Question 19

what is the age of onset for somatic tumors?

Answer 19

usually older

Question 20

what is the age of onset for familial tumors?

Answer 20

usually younger

Question 21

what is significant about Li Fraumeni

Answer 21

it breaks the rule that tumor suppressors are recessive - its a familial cancer associated with inheritance of a mutation of p53

Question 22

what is the lifetime risk of breast cancer

Answer 22

1/8