Molecular Testing in the Diagnosis of Cancer

Question 1

5 ideal drug target

Answer 1

• drives tumor growth
• turns on key mechanisms of cancer progression
• reversible by inhibition
• dispensable in normal cells
• target is measurable in tumor tissue used for diagnosis

Question 2

Molecular Diagnostic Methods

Answer 2

Real time pcr
dna sequencing
array

Question 3

challenge of molecular oncology testing

Answer 3

• normal genome vs. cell genome
• primary vs metastasis
• heterogeneity– tissue vs. tumor
• % tumor cell content
• recurrence- accurate testing of minimal residual disease
• monitoring

Question 4

Qualitative Testing

Answer 4

Diagnostic mutation analysis

ex) tracking of B and T cell rearrangements
ex2) HPV testing

Question 5

High risk forms of HPV

Answer 5

16, 17

Question 6

low risk forms of Hpv

Answer 6

6, 11-genital warts

Question 7

Quantitative Molecular oncology testing

Answer 7

minimal residual disease/tumor burden

ex) Chronic myelogenous leukemia– philadelphia chromosome and bcr-abl in 95% of cases

Question 8

Rx goals in CML (3)

Answer 8

1- hematological- normal pb value and spleen size
2- cytogenic response- reduction of ph+ cells in blood/bone marrow
3- molecular response- reduction or elimination of bcr-abl mrna in marrow or pb

Question 9

pharmacogenetics

Answer 9

use genetic informaton to predict drug response (metabolism) in patent with same dx taking a certain drug

Question 10

PGXm

Answer 10

studying metabolism- how fast person metabolizes drug

Question 11

PGXt

Answer 11

targeted treatment

Question 12

irinotecan

Answer 12

topoisomerase inhibitor used for colon cancer

Question 13

metabolism of irinotecan

Answer 13

CPT-11 (orally)–>SN 38 active form–> UGT1A1 (enzyme)–>SN 38 glucouronide (inactive)–>excreted

Question 14

mutation in UGT1A1 promoter

Answer 14

increase in TA repeats above 7–> BM toxicity & increased diarrhea

should use diff drug/lower doses

Question 15

syndromes where this mutation is seen

Answer 15

Criger-Najjar Type 1

Gilbert’s Syndrome (hyperbilirubinemia)

Question 16

immediate effects of chemo

Answer 16

extravasation
emesis
hypersensitivity
tumur lysis

Question 17

early effects chemo

Answer 17

myelosuppression
mucositis
alopecia
cystitis

Question 18

delayed effects chemo

Answer 18

cardiotoxicity
lung fibrosis
P. neuropathy
hepatotoxicity
nephrotoxicity

Question 19

late effects chemo

Answer 19

second cancer
encephalopathy
sterility
teratogenicity

Question 20

her2 gne

Answer 20

codes for an estrogen receptor linked to signal transduction pathways that promote cell replication
–35% breast cancers–>multiple copies her2–>more replication

Question 21

herceptin

Answer 21

a mAb specific for her2 to secreen breast cancers for increased her2 so that tamoxifen (a her2 antagaonist) can be used

Question 22

most common carcinoma in non-smokers

Answer 22

non-small celllung carcinoma

Question 23

what is special about non-small lung carcinoma?

Answer 23

conventional cytotoxic chemo has little effect

Question 24

EGFR

Answer 24

Receptor tyrosine kinase– two mutations make it constiuently active (fram del 19 and pt mutation 21)

if people have this mutation, can give anti-EGFR mAbs, but need to test to see if they have it first

Question 25

colorectal carcinomas with mutated KRAS

Answer 25

resistant to Rx with panitumamb

Question 26

KRAS mutations are associated with

Answer 26

smoking

Question 27

more about KRAS mutations

Answer 27

occurs most often in codons 12 and 13

missence mutations (change of amino acid)

7 common mutations

Question 28

successfully screening for more than 1 biomarker

Answer 28

high density microarray analysis

next generation sequencing