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Lecture

BIOL 314 - Definitions (Jabado's section)

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Department
Biology (Sci)
Course
BIOL 314
Professor
Thomas Duchaine
Semester
Fall

Description
Definitions: Tumor: An abnormal cell growth within a given tissue. Tumors arise from normal tissues: Ectoderm (neural & non-neural), Mesoderm or Endoderm. EMT: Epithelial-mesenchymal transition or transformation(EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. Carcinoma: Epithelial tumor Carcinoma in situ Basement membrane not breached, localized growth exclusively, best prognosis! Squamous cell External protective cell layers carcinoma: Adenocarcinoma Secreting cells Benign tumor Not cancerous, but can become malignant. Malignant tumor - Lack of Differentiation - Proliferation in situ, invasion of adjacent structures: (Basement membrane, then stroma.) - Ability to move and disseminate at a distance:metastasis - Creation of its own vascular network:neoangiogenesis Differentiation The process by which a less specialized cell becomes a more specialized cell type. Metastasis Ability to move and disseminate at a distance - Metastasis is an inefficient process, metastasis isoften specific to certain areas depending on the original cell. - Responsible for 90% of cancer deaths. Neoangiogenesis Creation of its own vascular network Anaplasia Completely dedifferentiated, very aggressive form of cancer. Progressive Progressive spreading of a cancer.Initially localized to a cell layer, Development disseminate locally, regionally then at a distance.Early detection can be very important for prevention. Adult Glioblastoma Most common CNS tumor in adults. Malignant brain tumor. Life expectancy is less than1Y. Extensive data on molecular aspects: Tumoral Genome, Tumoral transcriptome, Signaling pathways. Models of multistep process illustrate the links between cytogenetic (chromosomal) changes and disease stage Monoclonal growth. Tumors result from an initial monoclonal growth, meaning they arise from a single cell. Genetic changes accumulate during tumor progressionand make the cancer more aggressive. Prevention and treatment very important in most epithelial cancers (Colon, breast, prostate…) In some cases a single change may result in a tumor(CML, subset of pediatric cancers) Astrocytomas Type of brain cancer where progression seems unstoppable. Mesotheliomas Mesothelioma is a rare form of cancer that developsfrom cells of the mesothelium, the protective lining that coversmany of the internal organs of the body. Asbestos exposure is associated with mesothelioma in lungs. The rabbit of Used to prove chemical carcinogens. KY applied chemical onto Katsusaburo rabbit’s ear. Rabbit developed a tumor. Yamagiwa Proto-oncogene A normal gene whose protein product has the capacity to induce cellular transformation given it sustains some genetic insult. Oncogene The gene that has sustained some genetic damage and, therefore, produces an abnormal protein capable of cellular transformation and cancer. Wild type Allele that is the most frequently found in a givenpopulation. Selection of the one that is going to confer a survival advantage to the species. The other will be lost through time from the gene pool. coding DNA Encodes for a specific gene, only 1.5% of all DNA. 2% of the rest of the DNA is regulatory/”important” Junk DNA ~97% of the DNA, non-coding. Selected mutation Mutation in coding sequence, defective phenotype, loss of allele. Neutral Mutation Junk DNA, no effect, genetic polymorphism. Nucleosome Made of core Histones: H2A, H2B, H3, H4. Packages 147 bp of DNA H1 linker histone packages extra DNA between nucleosomes, making chromatin. H3 Core histone, involved in DNA repair, X inactivation, etc. DNA Stores genetic information. It is: - Organized; genotype/phenotype/coordinate expression/tissue specificity - Redundant: phenotype, homo-heterozygous, ploidy - Evolving: mutations, selection Housekeeping genes 10 000-15 000, needed for basic cell function. Tissue specific genes. <1000, contribute to differences between tissues. Gene expression Control the phenotype: patterns - What is going to be transcribed -which gene -which splice (alternative splicing) - When it is going to be transcribed -development -after - Where it is going to be transcribed -tissue specificity Transcription factors Small proteins binding to specific DNA sequences (Sequence motif) in Promoters and/or Enhancers Pleiotropic: One gene, many phenotypes. Multiple TF can govern the expression of a same gene. Expression program: Coordinated expression of genes within a cell Euploidy Normal chromosome spread. Aneuploidy Abnormal Chromosomes. Hypodiploidy Loss of chromosomes Hyperploidy Gain of chromosomes (up to Tetraploidy) Changes in Chromosome structure: Translocations Rearrangement of parts between nonhomologous chromosomes. Reciprocal An exchange of material between nonhomologous chromosomes. Translocations Amplifications (Or gene duplications) HSR (homogeneously staining region): amplificationof segments within the chromosome. Double minutes: Segments cleaving outside the chromosome and replicating autonomously Deletions Can involve: - Segments of chromosomes - Full chromosomes LOH Loss of Heterozygosity: Loss of one or several wild type or polymorphic alleles making the individual homozygous for a fragment of the chromosome including this (these) gene(s). Happens over a set of contiguous genes and markerson the chromosomes: regions of LOH Mechanisms: - Mitotic recombination - Gene conversion - Increased rate of LOH with increased endogamy Endogamy Mating with similar individuals, close to family, etc. Germ cell mutation Transmission to the offspring resulting in hereditary predisposition syndromes Somatic mutations Happen initially in one cell of any tissue except the germ cells. -No transmission to offspring - Multiplication leads to a cell clone: cancer is initially a clonal disease. CGH Comparative Genome Hybridization Compare DNA with probe. Helps detect ploidy. BAC array Used for CGH, stable cloning vector. SNP Single nucleotide polymorphisms Deep Sequencing Sequencing the whole genome. Immunohistochemistry Detect proteins using antibodies. Immunofluorescence Die proteins and detect with fluorescence microscope Loss of Heterozygosity Definitions: Acetylation: A reaction that introduces a functional acetylgroup into an organic compound. Deacetylation is the removalof the acetyl group. Acetylation is a post-translational chemicalmodification of histones, tubulins, and the tumor suppressorp53. Chromatin: The complex of DNA and protein that composes chromosomes. Chromatin packages DNA into a volume that fits intothe nucleus, allows mitosis and meiosis, and controls gene expression. Changesin chromatin structure are affected by DNA methylation and histonemodifications. CpG islands: Regions in DNA that contain many adjacent cytosineand guanine nucleotides. The "p" in CpG refers to the phosphodiesterbond between the cytosine and the guanine. These islands occur in approximately 40% of the promoters of human genes. Free of transposons, protected from mobile elements. DNA methylation: The addition of a methyl group to DNA at the 5-carbon of the cytosine pyrimidine ring that precedes a guanine. Genomic imprinting: The epigenetic marking of a locus on the basis of parental origin, which results in monoallelic gene expression. Histone: The main protein components of chromatin. The corehistones — H2A, H2B, H3, and H4 — assemble to form the nucleosome; each nucleosome winds around 146 base pairs of DNA. Thelinker histone H1 locks the DNA into place and allows theformation of a higher-order structure. Histone deacetylase: A class of enzymes that remove acetyl groups from an N-acetyl- lysine amino acid on a histone. Transposons: Sequences of DNA that can move around within the genome of a single cell. In this process, called transposition,the sequences can cause mutations and change the organization of DNAin the genome. Epigenetics: Histone modifications and DNA methylation. Affectsgene expression. Telomeres: Prevent DNA from being degraded. When telomeres are shortened, cells die. Cancer cells highjack telomerase to evade cell death. Histone Variants: • H3: seven variants • H4: one variant • H2: H2A; H2B; H2X • Linker histones ***Humans have 7 H3 variants Nucleosome Fundamental unit of chromatin. Hetero-Octamer. The nucleosome core particle is composed of histones comprising a tetramer of (H3-H4) 2lanked by two dimers of H2A-H2B, around which about 147 bp of DNA is wrapped. Canonical histones Provide the main supply of histones during replication. Produced exclusively during cell division. H3.1 and H3.2 arecanonical histones.
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