Module 7.1 Cancer Biology

Question 1

cancer

Answer 1

• group of diseases characterized by abnormal growth and spread of cells
• can develop in any part of body
• over 100 different types
• genetic disease mostly derived from single abnormal cell
• rates increase with age
• can inherit risk if mutation in germline cells (<10%)

Question 2

cancer cells

heritable properties (2)

Answer 2

1. they reproduce beyond normal restraints on cell growth and division
2. they invade and colonize territories normally reserved for other cells

Question 3

neoplasm

Answer 3

• means “a new growth”
• tumor caused by abnormal cell that grows and proliferates out of control
• somatic mutations and epigenetic changes
• benign = not invasive. removing or destroying mass locally usually completely cures it
• malignant = invasive secondary tumor (metastasis)

Question 4

apoptosis

Answer 4

• programmed cell death
• cell shrinkage and blooding, chromatin condensation, DNA fragmentation and degradation
• produces apoptotic bodies that immune cells can engulf and remove before contents of cell can spill out and cause damage
• happens during development and to remove old cells
• balances cell division to maintain homeostasis

Question 5

Philadelphia Chromosome

Answer 5

• smaller Chromosome 22 caused by translocation between long arms of Chromosomes 9 and 22
• breakage site and rejoining of translocated fragments is identical in all leukemia cells in any given patient, but site differs slightly from one patient to another
• cancer in each patient arises from unique accident occurring in a single cell

Question 6

cancer

somatic mutation causes

3

Answer 6

• DNA replication errors
• DNA damage by carcinogens (tobacco smoke, X-ray, UV, HPV)
• Hereditary risk factors

Question 7

epigenetic changes

Answer 7

persistent heritable changes in gene expression that result from modification of chromatin structure without alteration of cell’s DNA sequence

Question 8

tumor progression

Answer 8

1. Tumor initiates from single abnormal cell
2. Tumor evolves through repeated rounds of mutation and proliferation
   - more mutated cells increases chance of another mutation
   - mutated cells with selective advantage multiply
3. Proliferation of each clone hastens occurrence of additional mutation and tumor progression
   - creates dominant clone

Question 9

founder mutation

Answer 9

genetic alterations observed with high frequency in a group that is geographically or culturally isolated, in which one or more of the ancestors was a carrier of the altered gene

Question 10

mutations within tumor

Answer 10

many point mutations scattered over whole genome at rate of about 1 per million nucleotide pairs

Question 11

driver mutations

Answer 11

• Mutations that cause cells to become cancer cells and grow and spread in the body
• will be seen repeatedly in many different patients

Question 12

passenger mutations

Answer 12

• mutations that happen to have occurred in same cell as driver mutations due to the genetic instability
• irrelevant to the development of disease
• unlikely to be found in the same location in many different patients

Question 13

tumor subclone progression

Answer 13

• presumed founder of the cancer was already very different from a normal cell, but first split between branches occurred early when tumor was small
• large amount of additional changes within each branch.
• Cellular or environmental constraints (eg. treatment) put selection pressure on and cure most of subclones, while one or few subclones with resistance survive and thrive

Question 14

interchromosome rearrangement

Answer 14

• when two different chromosomes have become joined together

Question 15

intrachromosome rearrangement

Answer 15

sites of rearrangement found within a single chromosome

Question 16

cancer cells

genetic instability

causes

Answer 16

• defects in ability to repair DNA damage or to correct replication errors of various kinds
• defects in chromosome segregation during mitosis

Question 17

cancer critical genes

classes (2)

Answer 17

alteration contribute to causation or evolution of cancer by driving tumor genesis
1. proto-oncogenes (too much activity)
2. tumor suppressor genes (too little activity)

Question 18

oncogene

Answer 18

• mutations at same nucleotide position or exactly same nucleotide change found repeatedly across patients or across different cancer types
• gain of function mutation
• convert proto-oncogene (wild type) to oncogene (mutant)
• act in dominant manner
• single gene copy mutation can cause cancer
• can find through mutation hot spots: mutations at same nucleotide position or same nucleotide change

Question 19

tumor suppressor gene

Answer 19

• loss of function mutation
• generally behave in recessive manner
• function of both gene copies must be lost to drive cell toward cancer
• predominantly mutations that create stop codons, or indels that create frame shift

Question 20

proto-oncogene

oncogene conversion mutations

types (4)

Answer 20

1. Indel or point mutation in coding sequence
   - hyperactive protein made in normal amounts
2. Regulatory mutation
   - protein overproduced when mutation in regulatory region
3. Gene amplification
   - produce extra gene copies of WT protein during replication
4. Chromosome rearrangement
   - breaking and rejoining helix change protein coding region = hyperactive fusion protein
   - change control region of gene so that normal protein is overproduced

Question 21

hereditary retinoblastoma

Answer 21

1. inherited mutant RB gene
2. occassional cell inactivates its only good RB gene copy
3. excessive cell proliferation = retinoblastoma

• most develop multiple tumors in both eyes

Question 22

non-hereditary retinoblastoma

Answer 22

1. occasional cell inactivates one of its two good RB genes
2. occasional cell inactivates its only good RB gene copy
3. excessive cell proliferation = retinoblastoma

• 1 in 30,000 normal people develop one tumor in one eye

Question 23

RB gene

Answer 23

• tumor suppressor gene
• codes for RB protein, a universal regulator of the cell cycle, present in almost all cells of body
• acts as one of main breaks on progress through cell division cycle
• missing in several common types of sporadic cancer (carcinomas of lung, breast and bladder)

Question 24

tumor suppressor genes

inactivation causes (7)

Answer 24

1. nondisjunction causes chromosome loss during segregation
2. chromosome loss, then chromosome duplication
3. mitotic recombination event
4. gene conversion during mitotic recombination
5. deletion (WT allele removed)
6. point mutation (no longer WT allele)
7. epigenetic silencing (frequent)