LE5 College aantekeningen Oncology (NWI-BM015C) Hereditary Tumors

LE 5 – Hereditary tumors
November 24 t h , 2023

Oncogene
 Growth stimulating properties
 Gain of function mutations
o Activating mutation in one allele
 Hardly ever basis of tumor susceptibility (exception RET >MEN2A (thyroid carcinomas)).

Activating mutations




 Point mutation
 Amplification
 Chromosomal Translocation

Tumor suppressor genes
 Gatekeepers (RB1, TP53)
o Apoptosis: programmed cell death
o Senescence: permanent withdrawal from the cell cycle
 Caretakers (mismatch repair genes)
o Genome stability
 Loss of function mutations
o Inactivation of both alleles at cellular level
 Tumor susceptibility: inactivation of one allele in the germline
o Second hit:
 Loss of wild type allele (LOH)
 Epigenetic inactivation
 Mutation

, The Knudson two-hit model of tumor initiation




Knudson two-hit model in unaffected individuals