Unit 3 - Genetics

Front 1

Describe the mechanism of the ras protooncogene

Back 1

ras proto-oncogene encodes a G protein with GTPase activity; GTP normally activates the cell cycle; if ras is mutated, it can't cleave GTP and the cell cycle is never terminated

Front 2

Describe the mechanism of the RB anti-oncogene

Back 2

RB anti-oncogene is llocated on chromosome 13; encodes RB protein which binds to a gene regulatory protein (GRP); no expression of target genes whose gene products stimulate the cell cycle; cell cycle is repressed

Mutation of RB encodes abnormal RB protein that cant bind GRP; transcribed gene products stimualte the cell cycle; retinoblastoma forms

Front 3

Hereditary Retinoblastoma

Back 3

Inherited mutant copy of RB gene; mutation of the second copy of the RB gene occurs within many cells of the retina; multiple tumors in both eyes

Front 4

Nonhereditary retinoblastoma

Back 4

Individiual does not inherit a mutant copy of the RB gene; mutation of BOTH copies of the RB gene occurs within ONE cell of the retina; a SINGLE TUMOR DEVELOPS IN ONE EYE

Front 5

Describe the function of p53

Back 5

anti-oncogene; encodes for the normal p53 protein (zinc finger gene regulatory protein - GRP) which causes the expression of gene products which suppress the cell cycle at G1 by inhibiting Cdk2-cyclin D and Cdk2-cyclin E

p53 mutation encodes abnormal p53 protein that does not stimulate gene products which inhibit the cell cycle;

most common target for mutation in human cancers

Front 6

APC Gene (familial Adenomatous Polyposis Coli)

Back 6

APC anti-oncogene normally; mutation results in colorectal cancers

Front 7

Describe the histopathologic changes associated with specific genetic mutations in colon cancer

Back 7

Normal epithelium to small polyp: APC anti-oncogene mutation

Small polyp to large polyp: ras proto oncogene mutation

Large polyp to carcinoma to metastasis: DCC antioncogene, p53 antioncogene mutations

Front 8

HER2 (epidermal growth factor receptor)

Back 8

Overrexpression of HER2 is responsible for 25% of breastcancers

Blocked by tratsuzumab (herceptin)

Front 9

Abl oncogene function, mode of action, and associated cancers

Back 9

F: Nonreceptor tyrosine kinase
M: Translocation
Dx: CML

Front 10

C-myc oncogene function, mode of action, and aassociated cancer

Back 10

F: Transcriptional activator
M: Translocation next to Ig gene locus, so it becomes highly expressed. increases expresion of cyclin D)
Dx: Burkitt lymphoma

Front 11

BCL2 oncogene function, mode of action and associated cancer

Back 11

Anti-apoptotic protein; translation to region of high expression; B cell lymphoma

Front 12

Extrinsic Apoptotic Pathway

Back 12

Occurs with Fas ligand - Fas Death Receptor Interaction; activates procaspases

Front 13

Intrinsic Apoptotic Pathway

Back 13

stress, radiation or chemicals induce DNA damage ->p53 releases cytochrome c through the BAX channel (which is normally inhbited by anti-apoptotic bcl2) -> forms APAF -> caspase mediated apoptosis

Front 14

A mutation in APC (adenomatous polyposis coli) will cause a dysregulation of what protein

Back 14

B-catenin; levels will increase since APC normally downregulates it

Front 15

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

HNPCC normally does what

Back 15

Encodes for DNA repair enzymes; genetic instability if mutated

Front 16

Difference between carcinoma and adenoma

Back 16

Adenoma does not disrupt basement membrane
Carcinoma penetrates down through and beyond

Front 17

Why are consanguineous matings more likely to produce offspring affected with recessive diseases?

Back 17

Individuals who sare common ancestors are more liable to share disease causing mutations

Front 18

What is the gene frequency of an X linked recessive disease in the male population?

Back 18

It's the same as the incidence

If incidence = 1/3000 males then gene frequency = 1/3000 males