Chapter 10- Tumor Biology Flashcards
Most common HPV type causing h/n cancer
16
Driver mutations in thyroid cancers
Papillary: BRAF, RET
Medullary: RET
Follicular: PPAR-gamma-1
What Immunohistochemistry and FISH look for
IHC: Stain proteins
FISH: analyze for DNA translocations
Oncogene, Proto-oncogene, Tummor Suppresor Gene
Onco: confers potential to cause CA esp if overexpressed
Proto-Onco: normal gene, when mutated can contribute to CA
TSG: loss of fxn mutation keeps proteins from protecting a cell’s transition to CA
4 most common RF for HNSCC worldwide
Tobacco
Alcohol
HPV (esp 16)
Betel nut chewing (India, Taiwan, Papa New Guinea)
How HPV causes cancer
E6: oncoprotein, inactivates p53, no apoptosis
E7: inactivates Rb, promotes cell cycle progression
How p16 relates to HPV
Downstream of Rb
When Rb is destroyed by E7, p16 increases
So p16 is a way to detect HPV
Also can do FISH for HPV DNA in cancer cells
5 molecular pathways important in HNSCC
p53
EGFR (90% upregulated, RAS/MAPK, PI3K, angiogen, met)
PI3K (INC 6-20%, mTOR, cell grow, migrate)
NOTCH-1 (tumor suppressor, 12-15%)
Cyclin D1
Drug targeting EGFR
Cetuximab (Erbitux)
IgG1 Ab against EGFR extracellular domain
Keytruda
Pembrolizumab
Inhibits PDL-1
Allows immune system to target CA cells
Overexpressed receptors in salivary rumors
c-kit (proto-onc, grow, Adenoid Cystic 80-90%, mucoepidermoid (0-40%)
EGFR (AdCys, Mucoep, Adeno, Duct)
HER2/NEU (Duct, others)
Androgen receptor (Duct, Adeno)
Gene translocations salivary Ca
t(6:9) - MYB-NFIB Adeno is cystic
t(12;15) ETV-NYRK3 mammary analogue secretory Ca
t(11;19) CRTC-MAML2 mucoepi
Gene mutations PTC
RET (MEN-2)
NTRJ1
BRAF (MAPK)
Gene mutations FTC
PAX8 fusion protein
HRAS
PTEN
Gene mutations ATC
BRAF, TP53, PIK3, RAS
