Trigger 8: Epigenetics and cancers

Question 1

epigenetic-drven gene inactivation is at least as common as

Answer 1

mutational events which lead to cancers

Question 2

understanding how genetic and epigenetic alteration drive the initiation nd progression of cancer

Answer 2

will help foster new potential cancer biomarkers and therapeutic opportunities

Question 3

mutations in the epigenetic writers, readers and eraser

Answer 3

common in cancers

Question 4

mutations in members of chromatin-remodelling complexes

Answer 4

common in cancer

Question 5

mutations in the epigenetic regulators offer the cancer cell number of advantages

Answer 5

• require transcriptional programs

- adapt to environmental or therapeutic pressures

Question 6

which epigenome enzyme are commonly mutated in hematopoietic malignancies

Answer 6

DNMT3A and TET2

Question 7

DNA hypermethylation leads to

Answer 7

promotor silencing

Question 8

DNA hypomethylation leads to

Answer 8

genomic instability

Question 9

deamination of meCpG to TpG leads to

Answer 9

mutation

Question 10

DNA hypermethylation and hypomethylation and deamination all lead to

Answer 10

cancer

Question 11

DNA methylation plays a

Answer 11

critical role in carcinogenensis

Question 12

global hypomethylation

Answer 12

increase genomic instability

Question 13

de novo promoter hypermethylation leads to silencing of

Answer 13

tumour suppressing genes

Question 14

de novo promoter hypomethylation may result in activation of

Answer 14

porto-oncogenes

Question 15

hypermethylation and cancer effects

Answer 15

tumour suppressor genes

Question 16

name a tumour suppressor gene which is frequently altered in cancers

Answer 16

MLH1

Question 17

Epigenomics silencing of non-mutated MLH1 gene

Answer 17

mismatch repair protein- - frequently silenced by epigenetic in non-familial colon cancer

Question 18

mutated epigenetic machinery in cancer (acute myeloid leukaemia (AML)

Answer 18

DNMT3A and TET2

Question 19

Aberrant DNA methylation of multiple genes inc cancer related pathways

Answer 19

is a common event in carcinogenesis

Question 20

cancers can be classified according to

Answer 20

their degree of methylation

Question 21

CPG island methylator (CIMP) phenotype in cancer

Answer 21

= CIMP-associated cancers seem to have a distinct epidemiology, histology, and molecular features.

• The CIMP subtype has been documented in several additional cancers including prostate, glioma, leukaemia, and breast.

Question 22

combination of …… and …. in the hall marks of cancer

Answer 22

epigenetic modification and mutation

Question 23

screening for novel genes epigentially silenced inc ancer

Answer 23

identify novel cancer-related differentially methylated genes

validated using standard techniques such as QMSP and pyrosequencing

Question 24

cancer can be detected by

Answer 24

assessing DNA methylation

Question 25

DNA methylation has the potential to be an excellent cancer biomarker because

Answer 25

- DNA meth changes are common events in carcinogenesis - easy to detect with high sensitivity - DNAmeth is more stable than RNA or protein based markers

Question 26

examples of cancers which can be detected by DNA methylation

Answer 26

- prostate - lung cancer - colon cancer

Question 27

detection of cancer in cell free circulating DNA

Answer 27

molecular alterations found int tumour cells, such as methylation, is reflected in cell-free circulating DNA, released from tumour cell into the blood

Question 28

CircDNA is

Answer 28

an ideal candidate for the basis of blood-based cancer diagnostic tests

Question 29

prostate cancer gene

Answer 29

GSTP1

Question 30

Lung cancer gene

Answer 30

SHOX2

Question 31

colon cancer gene

Answer 31

Sept9

Question 32

deactivated hitsone

Answer 32

closed chromatin- gene silencing

Question 33

acetylation of histones

Answer 33

Abnormally open nucleosome configuration

Question 34

name the most clinically advances epigenetic therapies in oncology

Answer 34

DNA hypomethylating agents (DNMTi) Histone deactylase (HDAC) inhibitors

Question 35

DNA methylation inhibition

Answer 35

lacks specificity resistance is common not very successful in solid tumours

Question 36

HDAC inhibitors (HDACi) examples

Answer 36

Vorinostat

Question 37

DNMTi and HDACi have their greatest efficacy when

Answer 37

combined with other cancer therapies

Question 38

DNMTi is combined with

Answer 38

standard cytotoxic drugs in an attempt to resentisie cancer

Question 39

epigenitcs can also be used with

Answer 39

immunotherapy

Question 40

Cancer epigenetic research challenges

Answer 40

- how is heritable gene silencing in cancer cells maintained | - epigenetic biomarkers have low sensitivity and specificity

Question 41

when epigenetic biomarkers lack specificity

Answer 41

adverse side effects and off target affects