Genetics of Cancer Lecture 35
Genetics of Cancer Lecture 35
Alterations in different kinds of Genes cause Cancer Oncogenes dominant gain-of-function mutations promote cell transformation Tumor suppressor genes recessive,loss-of-function mutations promote cell transformation Mutator genes Usually recessive,loss-of-function mutations that increase spontaneous and environmentally induced mutation rates
Alterations in different kinds of Genes cause Cancer Oncogenes dominant gain-of-function mutations promote cell transformation Tumor suppressor genes recessive, loss-of-function mutations promote cell transformation Mutator genes Usually recessive, loss-of-function mutations that increase spontaneous and environmentally induced mutation rates
What chromosomal events convert proto- oncogenes to dominantly acting oncogenes Point mutations (e.g.,RAS) Partial deletion mutations (e.g.,RTKs) .Chromosomal translocations that produce novel fusion proteins (e.g.,Bcr-Abl) Chromosomal translocation to juxtapose a strong promoter upstream and the proto- oncogene such that it is inappropriately expressed (e.g.,cMyc,Bcl2) Gene amplification resulting in overexpression (e.g.,N-Myc)
What chromosomal events convert protooncogenes to dominantly acting oncogenes • Point mutations (e.g., RAS) • Partial deletion mutations (e.g., RTKs) •Chromosomal translocations that produce novel fusion proteins (e.g., Bcr-Abl) • Chromosomal translocation to juxtapose a strong promoter upstream and the protooncogene such that it is inappropriately expressed (e.g., cMyc, Bcl2) • Gene amplification resulting in overexpression (e.g., N-Myc)
Point Mutation Non-Dis junction LOH Loss of heterozygosity Chromosome Chromosome loss loss duplication wt l Rb Mutant Rb Recombination Interchromosomal Deletion Translocation Gene Conversion Recombination
Point Mutation Non-Disjunction Chromosome loss & duplication Chromosome loss Recombination Deletion Interchromosomal Recombination Translocation Gene Conversion wt Rb Mutant Rb LOH - Loss of heterozygosity
Sunlight Oxidation Pollution Food Cigarette Smoke Courtesy of Professor Bevin P.Engelward.Used with permission
Sunlight Pollution Oxidation Food Cigarette Smoke Courtesy of Professor Bevin P. Engelward. Used with permission