Lecture 4 - Cancer

Question 1

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?

Answer 1

somatic cells (ie typically not passed on to future generations);
typically due to individual genes (cytogenetic changes occur, typically later in disease progression)

Question 2

the ____ number is the most common chromosome number in a tumor population

Answer 2

modal

Question 3

cytogenetic defs:

the ____ line is the most basic clone of a tumor cell population

Answer 3

stem

Question 4

cytogenetic defs:

the ____ line is subclones derived from the stem line

Answer 4

side

Question 5

is stem line dependent on clone size or independent?

Answer 5

independent

Question 6

____ mutations appear to be random and occur as the cancer develops rather than causing/affecting progression

Answer 6

passenger

Question 7

____ mutations are mutated at high frequency in a cancer subtype and are involved in development/progression of cancer. name 2 general types

Answer 7

drive;

tumor suppressors, oncogenes

Question 8

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

Answer 8

metaphase;

G1

Question 9

proto-oncogenes are genes that are normally essential for cell _____. mutation in (one or two) allele(s) forms an oncogene?

Answer 9

growth/proliferation;

1 allele

Question 10

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 _____

Answer 10

inactive;
active;
point, GTP;
active

Question 11

Gene amplification may be cytogenetically seen as ____ _____ (small accessory chromosomes) or _____ _____ regions

Answer 11

double minutes;

homogenously staining

Question 12

an example of gene amplification causing cancer is ____ in neuroblastoma

Answer 12

N-MYC

Question 13

HER2-NEU:
is a \_\_\_\_\_;
mutation = \_\_\_\_\_\_;
found in breast and \_\_\_\_\_ cancer;
name of mono-clonoal antibody?

Answer 13

epidermal growth factor receptor like protein (EGFR);
amplification;
gastric;
trastuzumab

Question 14

burkitt lymphoma:

due to a t(__;___) usually, which causes activation of _____

Answer 14

8, 14;

C-MYC

Question 15

_____ lymphoma is characterized by t(14,18). what is on chromosome 18 and what does it do?

Answer 15

follicular;

BCL2 = anti-apoptotic gene

Question 16

______ is characterized by a t(9,22). forms a constitutively active ____ _____. treat with _____ which prevents excessive phosphorylation

Answer 16

CML;
tyrosine kinase;
gleevec (imatinib)

Question 17

telomerase:
lengthens the ____ strand by adding TTAGGG repeats to the __ ‘end of chromosomes to avoid loss of genetic material. often dysregulated in _____

Answer 17

lagging;
3’;
cancer

Question 18

MEN2A/B:
inheritance = _____;
due to ___ of function in ______;
cause what type of thyroid cancer?

Answer 18

autosomal dominant;
gain, RET;
medullary

Question 19

loss of function in the RET gene causes what?

Answer 19

hischsprung disease

Question 20

Retinoblastoma, inherited vs sporadic form:
multifocal tumors =
later onset =
bilateral =

Answer 20

inherited;
sporadic;
inherited

Question 21

Rb:
activation of cyclinD/CDK4 causes _____ phosphorylation of Rb. this causes release of _____ which is a transcription factor. this causes progression from ___ to ____

Answer 21

increased;
E2F;
G1–>S;

mutated Rb = can’t bind E2F = always activated E2F = increased cell proliferation

Question 22

Rb =
located on chromosome ___;
mutations cause increased risk for retinoblastoma and ________

Answer 22

13;

osteosarcoma

Question 23

_____ __ ______ = loss of normal allele from region of chromosome –> allowing defective allele on homologous chrome to become manifest. see in oncogenes or tumor suppressors?

Answer 23

loss of heterozygosity;

tumor suppressors

Question 24

name 2 types of “second hits” with loss of heterozygosit

Answer 24

chromosome loss;

somatic recombination

Question 25

p16 normally inhibits what?

Answer 25

phosphorylation of Rb by CDK;

so missing p16 = increased phosphorylation = increased transcription/cell growth

Question 26

Li-Fraumeni syndrome:
due to mutation in _____;
also known as SBLA syndrome bc it causes _______

Answer 26

P53;
Sarcomas, breast cancer, leukemia, and adrenal gland cancers

plus others

Question 27

with DNA damage, p53 binds to _____ and causes increased activity/production of _____. this inhibits ____ = _____ phosphorylation

Answer 27

DNA;
p21;
p21 inhibits CDK = decreased phosphorylation

== inhibits G1–>S progression

Question 28

p53 also induces apoptosis in damaged cells by upregulating _____.
p53 is located on chromosome ____

Answer 28

BAX;

17

Question 29

NF1 = due to mutation in gene that encodes for ______. this is a _____ activator that inhibits RAS normally.

Answer 29

neurofibromin;

GTPase (ie decreased GTP)

Question 30

NF2 is due to a mutation that encodes _____ ( ______ ) protein

Answer 30

merline;

schwannonomin

Question 31

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?

Answer 31

tumor suppressors;
DNA repair (nonhmologous end joining specifically);
ovarian;
BRCA2

Question 32

the fact that mutations in p53 and BRCA1/2 are associated with breast cancer is an example of ____ heterogeneity

Answer 32

locus

Question 33

Familial adenomatous polyposis:
inheritance = ______;
due to mutation of _____ which normally prevents ____ from driving cell division.

Answer 33

autosomal dominant;
APC (a tumor suppressor);
beta-catenin

thousands of polyps

Question 34

colon adenocarcinoma sequence:

mutation in _____ –> mutation in ______ –> mutation in ______ –> carcinoma

Answer 34

APC, KRAS, p53

Question 35

HNPCC:
due to mutation in what kind of genes?
inheritance = _____;
increased risk colon, ____, ____, and skin cancer

Answer 35

DNA mismatch repair (ie MSH, MLH)
autosomal dominant;
endometrial, ovarian

Question 36

what are microsatellites?

Answer 36

small blocks of DNA sequences repeated in tandem

Question 37

mutations in DNA repair leads to _____ or _____ of microsattelites aka microsatellite instability

Answer 37

expansion, contraction

Question 38

Xeroderma Pigmentosum:
inheritance = ______ _____;
due to problems with _______, which usually fixes ____ dimers formed by UV damage

Answer 38

autosomal recessive;
nucleotide excision repair;
pyrimidine

Skin cancer, intolerance to sun, etc.

Question 39

cocayne syndrome is caused by mutations that affect _____ ____ repair. of XP and cockayne syndrome, which repair is initiated by an RNA polymerase?

Answer 39

Transcription coupled;

cockayne

Question 40

epigenetic cancer:
DNA hypomethylation typically occurs at _____ sequences.
can lead to gain or loss of imprinting?

Answer 40

repetitive;

loss of imprinting (ie activates a oncogene)

Question 41

epigenetic cancer:
hypermethylation tends to occur where?
can cause silencing of _____ genes

Answer 41

CpG islands;

tumor suppressor