MOD first 3 lectures Flashcards

Question

2) mutation in TSG

Answer 1

eg RB | mutation means lose the brakes, causing cancer

Answer 2

eg p53 | mutation means cells that are supposed to die via apoptosis DON'T, so defective cells still multiply

Answer 3

eg BRCA | cannot fixed damaged DNA

Answer 4

Need mutations in lots of types of genes!

Answer 5

CML is associated with the philadelphia chromosome. this is when BCR from chromosome 9 translocates to ABL on chromosome 22, forming the Bcr-abl fusion on chrom 9:22 (bcr abl is an oncogene, and expresses an abnormal tyrosine kinase which cues abnormal growth signal)

Answer 6

- HPV 16 and 18 can cause squam cell carcin of uterine and oropharynx (most common) - Epstein barr virus (EBV, a herpes virus) can cause nasophar carcin and lymphoma (like burkitt) - HHV8 (human herpes virus 8) can cause kaposi sarcoma and lymphomas in AIDS pts - Hep B&C: hepatocell carcinoma

Answer 7

- H pylori: gastric MALT lymphoma and gastric adenocarcinoma | - Clonorchis sinesnsis: fluke that can cause bile duct carcinoma

Answer 8

WBC cancer! (can include enlarged lymph nodes etc)

Answer 9

germline mutation in APC (adenomatous polypsis coli) gene, a TSG), develop many colorectal ademonas early, need colectomy or eventually dev carcinoma

Answer 10

- Labile always profli (eg marrow) - permanent: non-dividing, dont give rise to neoplasms (eg neurons and cardiac myocytes) - quiesecent stable: in g0 phase, not dividing normally but can enter cell cycle or acquire mutations to give neoplasm (eg liver and renal tube cells)

Answer 11

1cm (palpation, xray), 1 billion cells, takes 30 divisions (exponential amplification)

Answer 12

proliferative pool, can be decr by chemo

Answer 13

``` # mitoses/fields= grade (proliferation/mitotic index PI and flow cyometry not done as much anymore) ```

Answer 14

Use antibodies to prolifreration markers, eg PCNA Ki-67 (MIB-1) is impt marker in BC (use an ab to this, so if ab binding shows 20% are ki-67 positive, this means theres 20% growth fraction, and these cells are prolif) -used to determine type of tumor, her-2 also

Answer 15

asymptomatic high WBC count painless lump, fatigue, wasting (cachexia), paraneoplastic syndromes (sx of immune resp against tumor)

Answer 16

any sx really, | carcinoid syndrome, hypercalcemia

Answer 17

Tumor cells rel serotonin, diarrh, bronchospasm, flushing/sweating, heart failure, GI tract and can flow to liver

Answer 18

squamous cell carcinoma in lung PTH like hormone rel by tumor cells abnormal clotting (trosseau's sign), clot, DIC (small vessel clots)

Answer 19

grade: differentation and number of mitoses, necrosis (higher grade =more aggro) Stage: tumor size/spread (MORE impt for prognosis!), higher stage means more extensive spread

Answer 20

- Monoclonal protein (immunoglobulin, myeloma (plasma cell cancer)/lymphoma) - Endocrine/hormones: increased lvls may mean tumor is secreting excess hormones - Serum tumor markers (elevated, shed into circ often by tumor in later stage)

Answer 21

CEA (carcinoembryonic ag; colon/pancr/lung carcin) AFP (alpha fetoprot; liver carcin, and testis/ovary/yolk sac tumors) PSA (prostate specific ag; prostate carcin) CA-19-9 (cancer ag; pancr adenocarcin) CA-125 (ovarian carcinomas)

Answer 22

Look @ histology from frozen section | Look @ cytology from needle aspiration or pap smear (less invasive)

Answer 23

carcinoma (keratin, int filament in epith cells)

Answer 24

Yes, but can still be fatal (so can hormone producing tumors)

Answer 25

DNA mutations that promote tumor development (mutations w no effect are passenger)

Answer 26

Primary: divide a limited amoutn of times before senescence Immortal: divide indefinitely Transformed: divide indef and other abnormal things like are indep of GFs, anchorage indep; immortal cells can become transformed and cause tumors

Answer 27

Incidence incr with age (so multiple events req) Transfection expts (introduce foregin DNA to transform cells and growth) Oncogene synergy (tumors dev faster if multiple oncogenes activated, eg both myc and fos) (cancer genes were also ID'd with transforming retroviruses, and genetic sequencing etc)

Answer 28

Protooncogene is normal gene that becomes oncogene when mutated TSG prevents tumor formation when activated

Answer 29

protoonco: need ONE mutation, gain of fxn (dominant), mutated allele not inherited (eg in germline) TSG: req TWO mutations, loss of fxn (recessive), often inherited (thru germline), if inherited usu has tissue preference

Answer 30

RB, APC | two mutations in these can cause inherited cancer syndromes

Answer 31

Can cause it to stay active in GTP-bound form and continually transmit growth signal (single base substitutions v common) May be issue with GAP (GTPase activating prot) causing issue with GTPase (which normally conv GTP to GDP)

Answer 32

extra chrom dna called double minutes, or in HSR (homogenously stained region)

Answer 33

c-myc 8:14 translocation, expressed constitutively

Answer 34

Point mutation (eg ras, SBS's) Amplification Translocation on chrom (eg bcr-abl) Insertion (Retroviruses ingtegrate near proto-onco, causing synth of abnormal prot, but rare)

Answer 35

1) Growth factors 2) Growth factor receptors 3) Signal transducers 4) Transcription factors 5) Inhibitors of apoptosis 6) Cell cycle regulatory proteins

Answer 36

overexpression of PDGF, TGF-a of EGF family, etc causing increased cell growth

Answer 37

bind growth factors and transmit growth signals via tyrosine kinase activity, eg Her2 receptor can mutate and be const activated, EGF R can have deletion etc

Answer 38

inner memb, transmit growth signals to cytoplasm prots eg Ras, activated by GNFRF/GEFs and GTP, inactivated by GAPs (???), and Akt (tyrosine kinase which prevents apoptosis and can increase activity if activated)

Answer 39

const active transcription of cell cycle stuff | eg Myc TF if increased then increases cell cycle prots and cancer

Answer 40

eg Bcl-2 overexpr decreases apoptosis, (preventing cytochrome C rel from mito, Bax induces apop)

Answer 41

eg cyclins combine with CDKs for cell cycle to progress, if cyclin D is overexpressed then faster cell cycle

Answer 42

``` point mut chrom transloc deletion/insertion DNA METHYLATION (whereas oncogenes are activated by above stuff and amplification), eg p16 TSG deleted/silenced ```

Answer 43

1) cell adhesion 2) Signal transduction 3) transcription regulators 4) DNA repair proteins

Answer 44

eg e-cadherin loss of fxn allows tumor cells to escape and metast (common in epith cancers)

Answer 45

NF-1 GAP that inactivates RAS by inr GTP hydrolysis, if lost then Ras is const active, icnr cell prolif Beta-catenin incr transcr /cell cycle w/ Wnt, where APC binds to beta-cat then causes degrad, loss of APC incr transcription and cell cycle progression)

Answer 46

Rb binds and inactivates TF E2F CDK can inactiv8 Rb to activate E2F by phosphorylating Rb (loss of Rb fxn inc transcr and cell cycle) Loss of p53 results in incr survival (normally would prevent dna dmg, incr p21 and bax -activates mdm-2, a protooncogene that inhibits own p53 fxn

Answer 47

- p16 is CDK inhibitor (inhibits cell cycle), loss of this causes cell cycle incr - ATM is a protein kinase activated by double strand breaks in dna, which phosphorylates and activates p53 causing cell cycle arrest, loss of ATM decr p53 activation - hMSH2 is dna MMR prot, loss causes accum of mutations

Answer 48

CLICKER Q's (molec aspects lecture) This year's notesets-review Practice q's (canvas, etc?) IMAGES (gross and histo) in neoplasia 1 lecture