Cancer Genetics

Front 1

Characteristics of Oncogenes

Back 1

- dominant--one mutational event required to contribute to cancer
- mutation results in gain of function
- mutations are somatic
- normal gene stimulates cell division
- protein kinases typical example

Front 2

Characteristics of tumor suppressor genes

Back 2

- ressive, require two mutational events to contribute to cancer
- mutant allele displays a loss of function
- inherited or somatic origin
- normal gene functions to restrain cell division
- transcription factors are examples

Front 3

How are oncogenes activativated?

Back 3

- gene amplification
- point mutations
- chromosome translocations

Front 4

Double minutes

Back 4

- extrachromosomal DNA fragments found in tumors
- circular chromatin which replicate during cell division
- actively transcribe proteins
- eg. Leukemia (C-MYC oncogene)

Front 5

Homogeneously staining regions

Back 5

- aka (HSR)
- amplified gene production due to multiple duplications of a chromosome region
- e.g. Neuroblastoma

Front 6

Comparative genomic hybridization

Back 6

- detects unbalanced chromosome changes in DNA
- test DNA is fluorescently labled green
- normal DNA red
- hybridization to normal metaphase DNA
- shifts towards red or green represent gain/loss of copy number
- balanced reciprocal translocations or inversions cannot be detected.

Front 7

Ras pathway

Back 7

- Growth factor binds to two transmembrane tyrosine kinase receptors
- receptors dimerize and autophosphorylate
- Receptors then bind Grb2 and SOS SOS is a GEF (guanine nucleotide exchange protein)
- SOS binds Ras, a monomeric G-protein anchored in the plasma membrane
- GDP on Ras exchanged for GTP
- Activated Ras binds raf, initiates MAP kinase pathway
- Ras is a GTPase, slowly deactivates itself.

Front 8

Cause of chronic myelogenous leukemia

Back 8

- chromosomal translocation t(9,22)
- ABL gene from chromosome 9 combines with BCR from 22
- new protein is formed with receptor tyrosine kinase binding activity
- cell is transformed
- Gleevec cures this by blocking tyrosine kinase receptor

Front 9

Burkitt lymphoma cause

Back 9

- transposition of a protein to an active chromatin domain
- Myc gene from chromose 8 transferred to Ig locus of chromosome 14
- Myc is transcribed along with Ig antibodies in active B cells
- common in central Africa & Papua New Guinea

Front 10

Li-Fraumeni syndrome

Back 10

- Multiple primary tumors
- dominantly inherited
- TP53 constitutional mutation
- TP53 is transcription factor which prevents damaged cells from progressing to S phase.
- cancer risk includes Osteosarcomas, leukemia, breast, brain, childhood adrenocortical tumors.

Front 11

Six acquired capabilities of a successful tumor

Back 11

- become independent of external growth signals
- become insensitive to external antigrowth signals
- become able to avoid apoptosis
- become capable of indefinite replication
- become capable of sustained angiogenesis
- become capable of tissue invasion and metastasis

Front 12

Familial adenomatous polyposis

Back 12

- autosomal dominant, chromosomally recessive
(2 hit)
- APC gene mutation through mismatch repair
(Associated Polyposis Conditions)

Front 13

Hereditary nonpolyposis colon cancer

Back 13

- autosomal dominant, chromosomally recessive
(2 hit)
- no preceding polyposis
- genes create a system that checks DNA for mismatched base pairs
- aka Lynch syndrome (prefered, since cancer is not restricted to colon)
- asending colon cancer predominates
- increased risk for stomach, urinary tract, small bowel, bile duct cancers

Front 14

Hereditary Breast and Ovarian Cancer

Back 14

- autosomal dominant
- BRCA1, BRCA2

Front 15

Cowden Syndrome

Back 15

- PTEN at 10q23
- cancer risk includes breast, thyroid, endometrial, mucocutaneous lesions, macrocephaly

Front 16

X-linked SCID

Back 16

- no T-cells nor NK cells
- B-cells present, but don't mature properly

Front 17

adenosine deaminase (ADA) SCID

Back 17

- B-cells and T-cells both absent
- NK cells present