Lecture 4 - Cancer Flashcards
are most gene mutations in cancer in somatic cells or germline cells? are most due to changes in individual genes or due to cytogenetic changes?
somatic cells (ie typically not passed on to future generations); typically due to individual genes (cytogenetic changes occur, typically later in disease progression)
the ____ number is the most common chromosome number in a tumor population
modal
cytogenetic defs:
the ____ line is the most basic clone of a tumor cell population
stem
cytogenetic defs:
the ____ line is subclones derived from the stem line
side
is stem line dependent on clone size or independent?
independent
____ mutations appear to be random and occur as the cancer develops rather than causing/affecting progression
passenger
____ mutations are mutated at high frequency in a cancer subtype and are involved in development/progression of cancer. name 2 general types
drive;
tumor suppressors, oncogenes
the _____ checkpoint in the cell cycle checks to see whether all chromosomes are attached to the spindle or not. the _____ checkpoint checks to see whether the enviornment is favorable for DNA synthesis
metaphase;
G1
proto-oncogenes are genes that are normally essential for cell _____. mutation in (one or two) allele(s) forms an oncogene?
growth/proliferation;
1 allele
RAS:
when bound normally to GDP, it is ____;
when bound to GTP it is ____;
a ____ mutation can cause it to be stuck in the ____-bound form and constitutively _____
inactive;
active;
point, GTP;
active
Gene amplification may be cytogenetically seen as ____ _____ (small accessory chromosomes) or _____ _____ regions
double minutes;
homogenously staining
an example of gene amplification causing cancer is ____ in neuroblastoma
N-MYC
HER2-NEU: is a \_\_\_\_\_; mutation = \_\_\_\_\_\_; found in breast and \_\_\_\_\_ cancer; name of mono-clonoal antibody?
epidermal growth factor receptor like protein (EGFR);
amplification;
gastric;
trastuzumab
burkitt lymphoma:
due to a t(__;___) usually, which causes activation of _____
8, 14;
C-MYC
_____ lymphoma is characterized by t(14,18). what is on chromosome 18 and what does it do?
follicular;
BCL2 = anti-apoptotic gene
______ is characterized by a t(9,22). forms a constitutively active ____ _____. treat with _____ which prevents excessive phosphorylation
CML;
tyrosine kinase;
gleevec (imatinib)
telomerase:
lengthens the ____ strand by adding TTAGGG repeats to the __ ‘end of chromosomes to avoid loss of genetic material. often dysregulated in _____
lagging;
3’;
cancer
MEN2A/B:
inheritance = _____;
due to ___ of function in ______;
cause what type of thyroid cancer?
autosomal dominant;
gain, RET;
medullary
loss of function in the RET gene causes what?
hischsprung disease
Retinoblastoma, inherited vs sporadic form:
multifocal tumors =
later onset =
bilateral =
inherited;
sporadic;
inherited
Rb:
activation of cyclinD/CDK4 causes _____ phosphorylation of Rb. this causes release of _____ which is a transcription factor. this causes progression from ___ to ____
increased;
E2F;
G1–>S;
mutated Rb = can’t bind E2F = always activated E2F = increased cell proliferation
Rb =
located on chromosome ___;
mutations cause increased risk for retinoblastoma and ________
13;
osteosarcoma
_____ __ ______ = loss of normal allele from region of chromosome –> allowing defective allele on homologous chrome to become manifest. see in oncogenes or tumor suppressors?
loss of heterozygosity;
tumor suppressors
name 2 types of “second hits” with loss of heterozygosit
chromosome loss;
somatic recombination
p16 normally inhibits what?
phosphorylation of Rb by CDK;
so missing p16 = increased phosphorylation = increased transcription/cell growth
Li-Fraumeni syndrome:
due to mutation in _____;
also known as SBLA syndrome bc it causes _______
P53;
Sarcomas, breast cancer, leukemia, and adrenal gland cancers
plus others
with DNA damage, p53 binds to _____ and causes increased activity/production of _____. this inhibits ____ = _____ phosphorylation
DNA;
p21;
p21 inhibits CDK = decreased phosphorylation
== inhibits G1–>S progression
p53 also induces apoptosis in damaged cells by upregulating _____.
p53 is located on chromosome ____
BAX;
17
NF1 = due to mutation in gene that encodes for ______. this is a _____ activator that inhibits RAS normally.
neurofibromin;
GTPase (ie decreased GTP)
NF2 is due to a mutation that encodes _____ ( ______ ) protein
merline;
schwannonomin
BRCA1/2:
are they tumor suppressors or oncogenes?
normally involved in what?
increased risk of breast and _____ cancer.
which increases risk of male breast cancer?
tumor suppressors;
DNA repair (nonhmologous end joining specifically);
ovarian;
BRCA2
the fact that mutations in p53 and BRCA1/2 are associated with breast cancer is an example of ____ heterogeneity
locus
Familial adenomatous polyposis:
inheritance = ______;
due to mutation of _____ which normally prevents ____ from driving cell division.
autosomal dominant;
APC (a tumor suppressor);
beta-catenin
thousands of polyps
colon adenocarcinoma sequence:
mutation in _____ –> mutation in ______ –> mutation in ______ –> carcinoma
APC, KRAS, p53
HNPCC:
due to mutation in what kind of genes?
inheritance = _____;
increased risk colon, ____, ____, and skin cancer
DNA mismatch repair (ie MSH, MLH)
autosomal dominant;
endometrial, ovarian
what are microsatellites?
small blocks of DNA sequences repeated in tandem
mutations in DNA repair leads to _____ or _____ of microsattelites aka microsatellite instability
expansion, contraction
Xeroderma Pigmentosum:
inheritance = ______ _____;
due to problems with _______, which usually fixes ____ dimers formed by UV damage
autosomal recessive;
nucleotide excision repair;
pyrimidine
Skin cancer, intolerance to sun, etc.
cocayne syndrome is caused by mutations that affect _____ ____ repair. of XP and cockayne syndrome, which repair is initiated by an RNA polymerase?
Transcription coupled;
cockayne
epigenetic cancer:
DNA hypomethylation typically occurs at _____ sequences.
can lead to gain or loss of imprinting?
repetitive;
loss of imprinting (ie activates a oncogene)
epigenetic cancer:
hypermethylation tends to occur where?
can cause silencing of _____ genes
CpG islands;
tumor suppressor
