Exam 3: Cancer II Flashcards
mutations in genes that control the cycle of cell division: control of the cell cycle
cyclin-dependent kinases (CDKs), cyclins
mutations in genes that control the cycle of cell division: G1 to S transition
retinoblastoma protein (RB)
mutations in genes that control the cycle of cell division: G2 to M transition
mitosis-promoting factor (MPF)
progression through the G2/M checkpoint is regulated by
cyclin B
signal-transduction pathways
- signals trigger a cascade of intracellular reactions producing a specific response
- Ras protein
receptors
inappropriate activation leads to dysregulation/stimulation of gene expression
The Ras signal-transduction pathway conducts signals from
growth factors and hormones to the nucleus and stimulates the cell cycle. mutations in this pathway often contribute to cancer
mutations in genes that control cell division =
oncogenes
how Ras works
binding of growth factor to receptor causes adaptor molecules bind and link Ras which binds GTP and becomes activated. activated Ras triggers a signalling cascade which causes active MAP kinase to move into the nucleus and activate transcription factors
genes that regulate telomerase
reactivation of telomerase expression helps protect chromosome ends
genes that promote vascularization help with the
spread of tumors
lynch syndrome
inherited disorder (autosomal dominant) that incr the risk of many types of cancer esp colorectal cancer. mutations in any of the DNA repair mech genes, ex MLH1, prevent the proper repair of DNA replication mistakes
mutations in genes that control cell division =
oncogenes; mutations can occur at any of the points during the cell cycle
spindle assembly checkpoint and cancer
abnormal chromosome # or aneuploidy; deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability.
colorectal cancer arises through the
sequential mutation of a number of genes (tumor progression model); mutations in multiple genes contribute to the progression of colorectal cancer. colon cancers are very treatable IF caught before metastasis
when telomere length is critically short _ stops
cell division
alterations to DNA methylation or chromatin structure are seen in may cancers; hyper/hypomethylation. reversible? are these mutations?
epigenetic changes for continued cell growth; changes in gene expression patterns. if they can change in somatic tissues, we can change them back. these are changes in chromatin structure so not mutations in traditional sense as not a change in DNA seq
genetic mutations in epigenetic modifiers in cancer
mutations in 3 classes of epigenetic modifiers (DNA methylation, nucleosome remodeling, and histone modification) is frequently observed in various types of cancers highlighting the crosstalk btwn genetics and epigenetics; the mutations of epigenetic modifiers probably cause genome-wide epigenetic alterations in cancer
t/f: incr # of genes being modified w/o genetic change (methylation of a tumor suppressor gene); changing the packing of chromatin has no impact in cancer progression
false; big impact in cancer progression
t/f mutations that alter chromatin may cause genome-wide epigenetic consequences that promote cancer growth
true; big contributor
genes that acquire traditional mutations (activation, deactivation, aa change) leads to
significant epigenetic modifications which leads to certain kinds of uncontrolled cell growth
_ is a general feature of cancer cells
chromosomal instability (genomic and chromosomal instability are the primary hallmarks of cancer)
types of chromosomal instability features
deletions, inversions, aneuploidy (chromosome # changes), and translocations
a _ translocation of chromosomes 9 and 22 causes _
reciprocal translocation that causes myelogenous leukemia; Bcr and Abl arms translocate which positions these 2 genes together and causes cancer (philadelphia chromosome)
a _ translocation of chromosomes 8 and 14 causes _
reciprocal translocation that causes Burkitt lymphoma; repositions Bcl2 (oncogene) behind a strong promoter, Bcl2 blocks apoptosis so when hyper activated, it prevents apoptosis from happening
the hallmark of follicular lymphoma is the
chromosomal translocation btwn chromosome 14 and 18 chromosomes; that lead to hyper-upregulation of Bcl2 expression in tumor cells
chromosomal translocation btwn 14 and 18 places
the Bcl2 gene next to the immunoglobulin heavy chain locus, making it constitutively active. Bcl2 encodes an integral outer mitochondrial membrane protein that blocks apoptotic death (ie cell fail to die) of cells such as lymphocytes and they propagate exponentially
Bcl2 is an important anti-apoptotic protein and thus classified as an
oncogene
cancer cells often possess chromosome abnormalities including:
extra chromosomes, missing chromosomes, and chromosome rearrangements
melanoma biomarkers
a fast rising cancer worldwide and validation of immunological biomarkers may have clinical applications in assisting prognosis, assessing endpoints in therapy, and monitoring responses during treatment
microRNAs and cancer
miRNAs are ubiquitous small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression; most cancers have inappropriately activated miRNAs that target tumor suppressor genes
miRNAs and chemotherapy resistance
miRNAs represent an alternative bc of genomic instability helps figure out a way for cancer cells to survive/natural selection impacting progression of disease; use our knowledge of miRNAs to target oncogenes/tumor promoting genes = novel therapeutic intervention
p53 is a _ gene
tumor suppressor gene and is the most frequently mutated gene (>50%) in human cancer
p53 becomes activated in response to myriad stressors:
DNA damage (induced by either UV, IR, or chemical agents) oxidative stress, osmotic shock, ribonucleotide depletion, and deregulated oncogene expression
statins and p53
through high-throughput screening, identify statins, cholesterol-lowering drugs, as degradation inducers for conformational or mis-folded p53 mutants w/ minimal effects of WT p53 and DNA contact mutants statins support elimination of mutated p53
why elephants do not get cancer?
elephants have close to 20 copies of p53 in their genome; animals that big usu have more mitotic events to get to their mass size and extra copies of p53 lead to elimination of cancer
why is cancer a genetic disease, but most are not inherited
cancer is the conseq of accum of mutations that overrides organism ability to inactivate these fast growing cells but despite that critical underpinning of cancer, there is still a lot of environmental contributions to cancer
