genetic basis of cancer

mendels overview

one trait → one gene → 2 variants (alleles)

in menders work what kind of dominance

complete

most human traits are polygenic meaning

• determined by interactions between multiple genes and the environment

genes overview

• genes determine phenotupe

• located on chromosomes

human chromosome 1 has around ____

2000 genes

the functional region of a chromosome

gene that codes for regions or functional mrna or proteins

gene regions

• direction of transcription

• can overlap with each other

• can go in the same or opposite strand.

homologous chromosomes

• two copies of each chromosome, one from each parent

gene sequences account for ______ of the genome

less than 5%

along the chromosome if it isn’t part of a gene

noncoding, junk intergenic regions

mb

• megabases

• a unit that measures in 1 million nucleotides

selected mutation

• mutation on coding sequence

• defective phenotyoe

• inability of organism carrying mutant allele to compete

• loss of allele from gene pool

neutral mutation

• mutation in the junk dna

• no effect on phenotype

• no reduction in ability to compete

• retention in gene pool

mutant alleles tend to be selected against or for?

against!

genetic polymorphisms

changes in non functional regions

• retained

mutant allele

• affect in protein product

• in coding region, in regulatory region

23 and me type of dna sequencing will pick up in

genetic polymorphisms based off of ancestry

23 and me like dna companies are or aren’t sequencing your whole dna

aren’t

• only at certain genes

give an example of conservation of gene sequence

• human protein sequence aligned with a corresponding protein produced by two yeast species

• last common ancestor over 2000 years ago

how do we number chromosomes on karyotypes

1 is the longest 22 is the shortest

centromeres in chromsomes via karotypes

• centromere is not in the exact middle

• shorter at the top

• longer at the bottom

karyotype in pancreatic cell example

mutations of chromosomes translocated to other areas

• changes at the genomic level are greater than those at oncogenes etc

• as cancer progresses the cancer cells undergo further mutations

different ways to visualize the human karyotype

• FISH

• scanning electromicroscope

• 
  

RNA polymerase II

• process of

epigenetics

• regulation of gene expression

• changes that affect gene expression without altering DNA sequence

example of epigenetics

• affect dna packaging

  • chromatin histone modification

    • acetylation, methylation, phosphorylation

  • dna - methylation

  • regulates access to the promoter

epigenetic of histone mod and dna mod

• called transgenerational

histological sections in tumors

• thin slices of tissue stained with different dyes or other reagents to reveal tissue architecture and components

histology is described as

microscopic analysis of sectioned tissues

histology can reveal

• overall tissue type

• types of cells present within the tissue

• surrounding supportive structures (stroma)

what defines the tumor type?

tissue of origin and cell type of origin

histopathology

• comparing diseased tissue to normal tissue

found in histopathology how can metastases be ID’d

• histological hallmarks of their original tissue of origin

why do epithelial tumors end up being 80% of cancer related deaths

more exposure to the elements and be influenced

benign tumor

grows locally does not invade adjacent tissues

malignant tumor

invades nearby tissues, spawns metastases

epithelial cell structure

• lumen (cavity)

• epithelial cells

• basement membrane (ECM)

• stroma

epithelia is described as

sheets of cells that line the walls, cavities and channels of our body as well as outside covering

epithelia have two major functions

• cells that serve to seal the cavity or channel they line

• cells that secrete substances into the ducts or cavities they line

squamous cell carcinoma

• come from epithelial cells that seal the cavity of channel they line

adenocarcinomas

• come from cells that secret substances into the ducts or cavities they line

connective tissue tumors

• called sarcomas

• 1% of tumors encountered

types of sarcoma

• osteosarcomas

• liposarcoma

• rhabdomyosarcoma

hematopoietic tissue tumors

7% of tumor associated mortality in the US

• lymphomas (solid tumor masses)

• leukemias (dispersed in circulation)

monoclonal tumors

• arise from one parent cell

• subsequent mutations create a heterogeneous tumor

a-typical tumors

• dont fit into other classifications/cells of origin unknown

types of a typical tumors

melanoma, small cell lung carcinoma, teratoma

monoclonal growths

• descended from a single cell

• as tumors grow, they get more mutations and become unstable

tumors and sub clonal growths

• as tumor cells accumulate mutations in different genes, tumors become heterogeneous

epidemiology and cancer

• incidence of specific cancers differs in different regions and genetic populations

tumor phenotype

• associated with alterations in genes

• usually more than one

exposure to carcinogens

• the more likely that there is mutation that causes cancer

carcinogens are mutagenic explain

• mutations do not have a preference for causing cancer (random)

• however the more exposure, the more mutations and likely they will

viruses and cancer

• are not random mutations

• can disrupt genomic DNA by insertion

• more common that a virus carries an oncogenic version of a gene

carcinogens causing cancer is not a good way to describe it explain

• it increases likelihood of mutations not necessarily directly causing cancer

the Philadelphia chromosome

• reciprocal translocation between human chromosomes 9 and 22

• responsible for a lot of chronic myelogenous leukemia