neoplasm 5 Flashcards
1
Q
define Gene APC
A
- function = prevents nuclear transcription
- associated with familial polyposis coli (adenocarcinoma of colon)
2
Q
define genes BRCA-1 and BRCA-2
A
- function = regulates DNA repair
- associated with breast and ovarian cancer
3
Q
define RB gene
A
- function = inhbits G1 to S phase
- associated with retinoblastoma and osteogenic sarcoma
4
Q
define WNT signaling pathway
A
- controls cell fate, adhesion and cell polarity during embryonic development
- self-renewal of hematopoeitic stem cells
- APC gene/B-catenin pathway is apart of WNT signaling pathway
5
Q
why is APC gene/B-catenin pathway important?
A
- APC protein down regulates B-catenin that prevents it accumulation
- inactivation of APC results in increase levels of B-catenin which results in B-catenin being translocated to the nucleus
- continuous WNT signaling causes FAP, non-familial colorectal CA and sporadic adenomas
6
Q
what are the cancers associated with Rb gene mutations
A
- retinoblastoma
- osteosarcoma
- soft tissue sarcoma
7
Q
describe Knudson’s two-hit hypothesis about retinoblastoma
A
- both allelles of Rb locus must be inactivated
- 1st hit in all somatic cells of the body (inherited from affected parent, other copy is normal)
- 2nd hit in retinal cells results in somatic mutation –> loss of normal RB gene –> causes retinoblastoma
8
Q
describe sporadic cases of retinoblastoma
A
- both normal Rb alleles are lost by somatic mutation in one of the retinoblasts
- cells homozygous for mutant tumor suppressor genes develop cancer
- recessive cancer genes = heterozygous cells are normal
9
Q
define p53 gene
A
- function:
- -> cell-cycle arrest at G1/S = acts via p21 (cyclin/CDK4 inhibition)
- -> apoptosis - induces pro-apoptotic genes (BAX)
- associated with lung, colon, breast Carcinoma
- associated with Li-Fraumeni syndrome
10
Q
describe HPV and p53
A
- HPV E6 inhibits p53 causing lack of apoptosis and excessive growth
- HPV E7 inhibits p53, p21 and RB-E2F causing lack of apoptosis and excessive growth
11
Q
describe VHL gene
A
- tumor suppressor gene located on chromosome 3p
- part of ubiquitin ligase complex
- -> regulates nuclear transcription via HIF-1a
- Associated with hereditary renal cell carcinomas (RCC), hemangioblastomas of CNS, retinal angiomas, renal cysts
12
Q
describe the warburg effect
A
- in the presence of ample O2, cancer cells demonstrate a distinct form of metabolism characterized by high levels of glucose uptake and increased conversion of glucose to lactose via the glycolytic pathway
- detected by PET (positron emission tomography) scan
- -> most tumors are PET positive
- -> rapidly growing ones are markedly PET positive
13
Q
describe the steps in carcinogenesis
A
- accumulation of successive mutations
1) normal epithelium loses APC
2) hyperproliferative epithelium loses DNA methylation
3) early adenoma has Ras mutation
4) intermediate adenoma loses DCC
5) Late adenoma loses p53
6) adenocarcinoma
14
Q
describe epigenetic changes
A
- epigenetics refers to reversible, heritable changes in gene expression that occur without mutation
- it involves post-translational modifications of histones and DNA methylation, both of which affect gene expression
- -> DNA methylation reduces expression and hisstone modifications lead to compaction of DNA into heterochromatin
15
Q
define carcinogenic agents
A
- agents that cause genetic damage and induce neoplastic change
- -> chemical carcinogens, radiation, oncogenic viruses/other microbes
