Genetic Basis of Neoplasia

Question 1

hallmarks of cancer

Answer 1

sustaining proliferative signaling by activating mutations in oncogenes

evading growth suppressors by deactivating mutations in tumor suppressor genes

enabling replicative immortality by preventing telomere shortening

activating invasion and metastasis by breaking BM and invading the ECM

inducing or accessing vasculature to have blood vessel growth to the tumor to provide nutrients and O2

resisting cell death by mutating apoptotic genes or over-expression of anti-apoptotic genes

Question 2

extrinsic causes of cancer

Answer 2

environmental exposure: gamma irradiation, UV light, second-hand smoke, chemicals

infectious agents: viruses (papillomaviruses, retroviruses) and other infectious agents

Question 3

how do retroviruses cause cancer?

Answer 3

activate oncogenes by insertional mutagenesis

become acutely transforming oncoviruses (part of viral genome is replaced by a cellular proto-oncogene)

Question 4

intrinsic causes of cancer

Answer 4

genes- cancer is an acquired genetic disease

genes involved are proto-oncogenes and tumor-suppressor genes

also apoptosis genes and DNA repair genes

Question 5

proto-oncogenes

Answer 5

normal regultatory genes that promote cell growth
can become oncogenes leading to unregulated cell growth when mutated or expressed at high levels

*oncogenes can also be activated by chromosomal translocations where you place a proto-oncogene under control of a constitutively active promoter

oncogenes are always dominant- only need one mutated copy to get uncontrolled cell growth

Question 6

examples of proto-oncogenes

Answer 6

growth factor receptors
transcription factos
cell cycle regulators

Question 7

tyrosine kinase c-Kit

Answer 7

example of growth factor receptor affected in mast cell tumors of dogs

drugs used are tyrosine kinase inhibitors (palladia, kinavet, gleevec)

Question 8

tumor-suppressor genes

Answer 8

normal genes that suppress cancer growth

mutations in TSGs are recessive- both alleles need to be inactivated to predispose to cancer

ex: p53, Nf-1, retinoblastoma

Question 9

p53

Answer 9

a transcription factor that regulates expression of genes that block cell cycle or induce apoptotic cell death

activated in reponse to cell damage or adverse environment

mutations lead to a failure to halt cell cycle (inability to bind to target genes p21, Bax, and GADD45)

Question 10

retinoblastoma RB

Answer 10

prevents excessive cell growth by inhibiting cell cylce by sequestering E2F

mutations lead to uncontrolled cell growth and retinoblastoma

Question 11

NF-1

Answer 11

transcription factor that accelerates GTP hydrolysis to GDP thus inactivating Ras

mutation leads to neurofibromatosis marked by constitutive Ras activity