Wk 3 Tumorigenesis

Question 1

6 hallmarks of cancer

Question 2

What is variance?

Answer 2

it takes multiple aberrancies to become a tumor - multistep carcinogenesis
-many paths to get to cancer from a normal cell, each with multiple “hits”

Question 3

How are pediatric cancers different from adult cancers?

Answer 3

1. mutations w/in developmental programs (retinoblastoma - Rb)
2. can be same # hits, but happen earlier (sometimes starting in germline) and in rapidly dividing cells
3. often arise from stem/progenitor cells (balstomas, leukemias, Ewing’s sarcoma)

relatively rare: ~8k pediatric vs 250k breast cancer

Question 4

What are 2 categories of mutations w/ tumorigenesis?

Answer 4

1. gain of function - growth signals (accelerator pedal), angiogenesis, tissue invasion metastasis
2. loss of function - anti-growth signals (brake pedal), senescence, apoptosis, immunity

Question 5

What are signals that cause cells to grow?

Answer 5

Secreted factors (autocrine or paracrine – e.g. EGF)
Activation/mutation of growth receptors (e.g. EGFR)
Activation/mutation of downstream signaling molecules (e.g. Ras, Raf, PI3K) or
transcription factors (e.g. Myc)

Question 6

What are anti-growth signals?

Answer 6

Cell cycle regulation/checkpoints (e.g. p53, Rb)
Soluble factors
Extracellular matrix
Cell-cell contact inhibition
Differentiation

Question 7

2 major molecular events (mutations) that contribute to cancer

Answer 7

1. activation of oncogenes
2. loss of tumor suppressors

Question 8

Diff b/w activation of oncogenes and loss of tumor suppressors

Answer 8

Oncogene acts dominantly (single allele sufficient) to initiate tumor formation
Both copies of TS genes (recessive) need to be inactivated by mutation for abnormal cell growth to result