Genetics Ch 19

what is the difference between genetic and inherited?

genetic: issue with genetic material, all cancer is genetic
inherited: issue with genetic material passed on from parents (gremlin cells)

where does the majority of cancer come from?

90-95% comes from somatic cells
a predisposition to cancer can be inherited, cancer itself is usually not inherited

define tumorigenesis

malignant transformation from a normal cell to cancer cells after exposure to a mutational event
need a long series of mutations to actually be cancer

what are the hallmarks of cancer?

sustaining proliferative signaling
evading growth suppressors
activating invasion and metastasis
enabling replicative immortality
inducing angiogenesis (get blood)
resisting cell death
must meet all to be cancer

what is the primary cause of melanoma in humans?

thiamine dimers
the damage leads to mutation when it is fixed wrong or replicated when damaged

what is progression?

continuing change over time of a cancer cell population causing them to become more malignant, more aggressive, and less normal in appearance, function, and growth regulation

what genomic alterations are associated with cancer?

single-nucleotide substitutions to large-scale chromosomal rearrangements, amplifications, and deletions

describe the chromosomal defect of chronic myelogenous leukemia (CML)

C-ABL gene on chromosome 9 is translocated into the BCR gene on chromosome 22, becoming the BCR-ABL protein
this causes an abnormal signal transduction molecule (phosphoration of proteins by kinases is important mechanism in communicating signals within a cell)
CML cells stimulate cell proliferation even in the absence of external growth signals

what is P53?

one of the primary genes that makes sure a cell goes through apotheosis if necessary

what turns P53 on?

generally inactive, but under stress levels increase and becomes active transcription factor, due to release of MDM2
MDM2 adds ubiquitin onto P53 in unstressed cells (degradation)
the presence of active P53 triggers negative feedback loop that creates more MDM2 protein, which rapidly returns P53 to its rate and inactive state

what are cyclins and cyclin-dependent kinases (CDKs)?

mediates cell cycle progress
regulate synthesis and destruction of cyclin proteins
mutations to these or anything controlling cell cycle can cause cells to continue to grow and divide without repairing DNA damage

what are the two categories of cancer causing genes?

proto-oncogenes and tumor supressor genes

what are photo-oncogenes?

normal cells that regulate cell cycle, increase activity
encode transcription factors that stimulate expression of other genes
signal transduction molecules that stimulate cell division: bucket brigade, molecular signal brigade that deliver growth factors to receptors on the cell membrane
cell cycle regulators that move the cell through the cell cycle

what is an oncogene?

when the proto-oncogene gets mutated, becomes oncogene
excessively or inappropriately active version of normal prototype-oncogene

describe tumor suppressor genes

genes that code for products that regulate cell cycle checkpoints or initiate the process of apoptosis
normal response is proteins halting progress through cell cycle in response to DNA damage or growth suppression signals
both alleles must have variant

what silences tumor suppressor genes?

inactivation of promotor
early stop codon
DNA methylation in the promotor region that inhibits transcription
aneuploidy
dicer syndrome

how do suppressor gene products regulate cell growth?

limiting/inhibiting expression of oncogenes
inducing apoptosis when needed

describe oncogenes at the cellular level

dominant at cellular level, only one proto-oncogene has to become an ocogene for tumorigenesis

what has to happen to tumor suppression genes for tumorigenesis to occur?

both alleles have to be mutated/lose function
if only one, it can still create gene product, but can lead to a decrease monitoring, leading to increased chance of further genomic changes

what actually causes cancer?

genetic predisposition, environmental factors, and viruses

what are some viruses that contribute to cancer?

retroviruses (RNA virus): integrate into host genome as provirus that is replicated with the host's DNA during the normal cell cycle

what are three ways a retrovirus can cause cancer?

proviral DNA may integrate near one of normal prototype-oncogenes and stimulate high levels or inappropriate timing of transcription of prototype-oncogenes
acute transforming retroviruses pick up a copy of a host photo-oncogene and integrate it into its genome (can mutate during transfer and create tumor cells)
normal retrovirus with normal viral gene products stimulate inappropriate cell growth`

describe inherited cancer-susceptibility

most from somatic variants, but some hereditary cancers are known
most inherited cancer-susceptibility alleles are not sufficient in themselves to trigger cancer development
at least one somatic variant in the other copy of the gene must occur to drive cell towards tumorigenesis (two hit hypothesis)

what causes sporadic cancer?

environmental factors or unknown
no observable pattern of inheritance

what are interfering RNAs?

natural phenomena that evolved to defend cells against viral invasion
method of gene blocking, that when compromised can be a cause of cancer
many viruses produce double stranded RNA

list the types of interfering RNA

siRNAs: short interfering RNAs
RISC: RNA induced silencing complex
miRNAs: micro RNA
RITS: RNA induced transcription silencing

when can short RNAis be produced?

happens during Dicer syndrome, causes abnormal gene expression