Solid Tumor Flashcards
What gene is associated with PTC (2 of them)?
Follicular?
RAS is associated with?
PTC: BRAF V600E (not seen in benign or folicular)
PTC: RET-PTC 1-9; specific for PTC
Follicular: PAX8-PPAR gamma t(2-3)
RAS: PTC, Follicular Carcinoma and adenomas
EGFR mutation associated with TKI Resistance?
Other EGFR mutations that are less commen?
What can be amplifed to make EGFR inhibitors no longer functioning?
EGFR T790M; needs Tagrisso/osimertinib
Others: T854A, D761Y, and L747S
Also: MET amplification
In Diffuse astrocytoma’s with IDH mutations what other 2 genes are lost/mutated?
IDH 1 R132H makes?
ATRX lost and TP53 mutated
2-hydroxygluterate
Cancer syndromes tend to be caused by mutations in what?
What time of gene has more specific mutations associated with cancer?
Tumor Supressor Genes and inheriting one bad copy
Onocogenes: Many have multiple mutations and not just a hot spot like in an oncogene
Harder to turn off; can be activated
What codon KRAS is associated most with Colon Adeno?
Mechanism of KRAS mutation?
What percentage are BRAF V600 mutated?
2 Anti-EGFR drugs; do they work if KRAS is mutated?
KRAS exon 2 codon 12 and 13; WT=better prognosis
Increases affinity for GTP and decreased hydrolysis increasing activity of BRAF
8%; poor prognosis and decreased response
Anti-EGFR: cetuximab or panitumumab, (surface recepotor needs to be WT); NO!!
BCRA 1 and 2: Percent Jews who carry, non-Jews?
What tyoe of breast cancer do they see?
10% Jews and 2-3% non-Jews|
Medullary and Triple Negative
Lynch Colon Cancer what genes are most commonly mutated?
HNPCC histology; side?
What other test do you need to do if MLH1 and MSH2 are mutated?
If MSI-H what gene mutation is ruled out?
MLH1 and MSH2 (90%), MSH6 (5%), PMS2 (<2%)
Pooly differentiated and medullary type (highly specific 90%); Right
MSH1 methylation!
BRAF mutations in MSI-H are very rare
Lung cancer EGFR Mutation? What population?
Exon 20 resistance mutation; what other gene can be amplified?
Drugs for EGFR wild type?
Exon 21 L858R and Exon 19 (indel); Young female non smokers
5% get Exon 20 T790M; MET amplifications
Afatinib, Erlotinib, Gefitinib (TKI–needs WT EGFR)
ROS1 is a translocation with at what end?
Population?
Drug?
3’ end of ROS one with TKI; lots of partners
1% NSCLC, younger never smokers
Crizotinib
Lung ALK is what translocation?
Can you use EGFR drugs?
EML4-ALK; Alk on 2p; female, Asian, non-smokers
NO!!
Common melanoma mutations?
First Gen Drug to tx?
More recent drugs?
BRAF (V600E most common)
Vemerafernib for V600E and K; side effect can cause SCC
Dabrafenib (BRAF inhibitor) Trametinib (MEK inhibitor)
GIST mutations?
What exons?
What drug can target; what exon needs highest dose?
KIT
Exon 11 (juxtamembrane 70%), Exon 9 (extracellular); Exon 13/17 Imatinib (TKI); Exon 9 needs higher dose
GIST that are KIT negative tend to have what mutations?
Exons?
Drug to treat; what mutation has poor response?
PDGFRA 8%
Exon 12 (extracellular), Exon 14 (kinase), Exon 18 (kinase)
Imatinimb again; D842V
BRAF mutations seen in what type of thyroid cancer?
RET translocations also seen in?
PAX8-PPAR gamma t(2;3) seen in?
RAS mutations seen in?
PTC; highly specific!; found in 50% (not sensitive)
RET: PTC; (1-9); 1% in follicular adenomas
PAX8-PPAR g: Follicular cancer
PTC, onvential PTC and some follicular cell; Not specific to any one thing
IDH should make what product?
What mutation; product?
Commonly seen in what CNS issues?
IDH mutation prognosis?
Isocitrate to alphaketogluterate
Makes D-2hydroxyglutarate (bad); IDH1 R132H
Grade II-III astrocytomas and oligodenndrogliomas and seoncdary GBM
TERT mutations are associated with good or bad prognosis in CNS?
Are these mutations in gene or in promoter region?
Bad
Promoter region
Trametinib is a drug for?
Erlotinib, Gefitinib and afatinib are what kind of drug?
Osimertinib is what kind of drug?
MEK inhibition
1st and 2nd gen TKI’s
3rd Gen TKI; anti-EGFR that can overcome p.T790M
Uveal melanomas harbor mutation in what 3 genes?
FISH for bladder cancer looks at what chromosomes?
GNAQ, GNA11, and BAP1
3,7,17, 9q21
MSS stable Colorectal cancer should be tested for what genes?
BRAF, KRAS, and NRAS
Hep C IL28b; what mutation is better response to treatment?
Affects what drug?
Encodes IFN-lambda-3;
C: better response higher viral load but quicker to clear
T: Worse response; lower baseline load
Pegylated Interferon/Ribavirin
Hep B procore mutation and effect?
G1896A; stop codon in procore regioin (B-G, rare A)
Acquisition of preC G1896A results in lower rates of chronic liver disease
Genotype A needs a C at 1858 so no loop forms
What is a positive HER2 amplifcaiton (HER2:CEP17 ratio)?
Equivocal?
Negative?
FISH HER2 amplificaiton: FISH ratio >2.2 or HER2 gene copy greater than 6.0
FISH ratio 1.8-2.2 or HER2 gene copy 4.0-6.0; count recount
FISH ratio <1.8 or HER2 copy less than 4.0
