The Biology of Cancer Second Edition Robert A
The Biology of Cancer Second Edition Robert A. Weinberg
Chapter 1: The Biology and Genetics of Cells and Organisms
Charles Robert Darwin (1809 ~ 1882) 1859
Natural selection: the nonrandom process by which biologic trait become either more or less common in a population as a function of differential reproduction capacity and adaptation ability to environment Darwinian fitness: the ability to survive and reproduce
Gregor Johann Mendel (1822~1884)
Basic rule of genetics: Genetic information is organized in discrete packets
Incomplete dominance
Terms to know - Allele (allelomorph): One of two or more forms of a gene or a genetic locus, resulting in observable phenotypic traits. - Gene : a molecular unit of heredity of a living organism. - Phenotype : an organism’s observable characteristics or traits such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior. - Genotype: the inherited instructions carried within its genetic code
- Karyotype: the number and appearance of chromosomes in the nucleus of an eukaryotic cells. The term is also used for the complete set of chromosomes in a species, or an individual organism - Ploidy : the number of sets of chromosomes in a biological cells. - Homozygous - Heterozygous - Hemizygous - Euploid : the normal configuration of chromosomes - Aneuplody : deviation from the euploid karyotype
Dominance and recessiveness of certain genes informed from the development of tumors
Molecular evolution (Non-Darwinian Evolution) : The Neutral Theory ü The vast majority of evolutionary change at the molecular level are caused by random drift of selectively neutral mutant (not affecting fitness) ü The vast majority of molecular differences are selectively “neutral”, i. e. the molecular changes represented by these differences do not influence the fitness of the individual organism ü Most evolutionary changes is the result of genetic drift acting on neutral alleles
Human genome is composed of small portion of important sequences (~ 3. 5%) and junk DNA
Neutral mutation and evolution
Polymorphic diversity in the human gene pool
Types of genetic variations : - Single nucleotide polymorphism (SNP) - Microsatellite loci such as (CA)n repeat - Inversions, translocations, deletions or duplications, and existence of transposable elements at a particular locus in the genome - Insertion-deletion polymorphism (indel) - SNPs in mt. DNA and cp. DNA
Certain genes are highly conserved during evolution
Localization of genes along chromosomes
Physical maps of human sex chromosomes Barr body
Chromosomes are altered in most types of cancer cells SKY analysis
Aneuploid karyotype of human pancreatic cancer cell Reciprocal translocation m. FISH
Human hepatocellular carcinoma cell line
Mouse breast cancer cells Amplified Her 2/Neu oncogene on double minute (DM) chromosomes
COLO 320 (human neuroendocrinal tumor cells) Amplified myc oncogene on DMs and HSR Interstitial deletion caused by radiation from plutonium
Germ line vs. somatic mutations in cancer development
Genotype embodied in DNA sequences creates phenotype through proteins: Intracellular and extracellular scaffolding
Cell motility
Protein structures and multiprotein assembly
Processing of pre-m. RNA
Gene expression patterns also control phenotype
Histone modification and Transcription factors control gene expression
Epigenetic control of heritable gene expression
Control of gene expression by RNA interference
Molecular cloning of genes: revolution in the study of normal and malignant cells
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