Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Clinical Genetics > Clinical Cancer Genetics > Flashcards

Clinical Cancer Genetics Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

How is genetic info encoded?

A

Genetic info is encoded by DNA

Stretches of DNA codes for genes which are packaged into chromosomes present in every cell nucleus in the human body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the importance of genetic in cancer?

A

Significant for detecting people with an increased lifetime risk of developing cancer due to genetic factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is cancer risk reduced in those with cancer genetic risk?

A

To reduce their risk of cancer due to genetic risk we submit them into the following programmes:

  • Screening
  • Prevention
  • Early detection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is DNA?

A

Deoxyribonucleic acid (DNA) is a molecule encoding the genetic instructions used in the development and functioning of living organisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What 4 bases form DNA?

A 
Made up of 4 nucleotides or “bases”
A = Adenine
T = Thymine
C = Cytosine
G = Guanine

Runs in 5’ –> 3’ direction
opposing strand is 3’ –> 5’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are genes?

A

Consist of sections of DNA which the cell translates into proteins
Genes tell the body how to grow, develop and function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How many genes are there in humans?

A

~ 20,000 genes in the human genome

2 copies of most genes – one on each chromosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the human genome?

A

The entire length of DNA contained in human cells; 3 billion bases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How many genetic variants are there from person to person?

A

We have ~5million different genetic changes compared to another unrelated person

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the use of genetic variation?

A
  • Makes us unique “polymorphisms”
  • Basis for evolution
  • Basis for disease
  • Caused by intrinsic errors in DNA replication and repair
  • Caused by external factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How odes genetic variation affect disease?

A

Genetic variation may influence our chance of developing disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the changes in normal cell division that occur leading to cancer

A

Normal cells divide, replicating their DNA before division

DNA replication is complicated and results in errors in a gene/s (i.e. a somatic mutation)

Normal cells die when an error cannot be repaired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does cancer arise from incorrect cell replication?

A

Cancer results when mutations accumulate, cell does not die and cell growth is uncontrolled

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How common is cancer?

A

Cancer is a common disease in humans

There is a 1 in 2 lifetime risk of developing cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What causes cancers?

A

Most cancers caused by combinations of genetic, environmental and lifestyle factors – multifactorial/sporadic - due to acquired (somatic) mutations within a cell giving it a growth advantage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What % of cancers are due to inheritance?

A

Only ~5-10% of cancers are due to the inheritance of a single cancer susceptibility gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do somatic mutations arise?

A

External factors like smoking, exposure to UV causes a permanent change to the DNA, known as a mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is a somatic mutation?

A

Somatic mutations are just in that one cell but not in every cell in the body
Mutation in tumour only (e.g. breast)
- Occur in non germline tissues
- Non Heritable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How many of the genetic variations normally occurring from person to person are de novo?

A

5 million differences per person

10,000 of those variants will be in protein coding genes of those, about 40-100 will be de novo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are germline mutations?

A
  • Present in egg or sperm
  • Inheritable
  • Cause cancer family syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Outline features of sporadic cancers

A
  • No increased risk of other cancers
  • Usually small increased risk to relatives
  • No genetic testing indicated
  • Normal clinical management for affected individuals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe the features of hereditary cancers

A
  • High risks of recurrence/other associated cancers
  • High cancer risks in relatives
  • We can offer testing to at risk individuals
  • We can offer screening and preventative management to gene carriers
  • May alter treatment of affected individuals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why are most cancers sporadic?

A

Most cancers are sporadic due to acquired mutations which only occur in cancer cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What causes hereditary cancers?

A

A smaller proportion of cancers are due to inherited genetic changes

  • Multiple lower risk genetic variants; multifactorial / polygenic risk
  • Single high risk genetic variant in a cancer predisposition gene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How common are high risk CPGs?

A

High risk cancer predisposition genes are very rare within the population but if present is very likely to cause cancer e.g. Tp53 mutation = 9/10 cancer risk

26
Q

How likely are common variants to cause cancer?

A

Common variants in the populations are less likely to cause cancer alone, but higher numbers of common variants increase the risk of cancer development

27
Q

How common are multifactorial risks?

A

Multifactorial cancer risks are very common

There is an increased multifactorial risk where there are clusters of the same types of cancer

28
Q

What causes multifactorial risks to occur?

A

These are due to SNPs (single base mutations) that are more common in cases than controls - can test for these

29
Q

What is reduced penetrance?

A

The idea that NOT every person with a germline mutation develops the disease

30
Q

Give examples of the high risk cancer predisposition genes (CPGs)

A

High risk cancer predisposition genes:

  • Breast cancer 5-10%
  • Ovarian 10%
  • Colon 5-10%
  • Melanoma 10%
  • Medullary thyroid25%
  • Retinoblastoma 40%
  • Prostate 5-10%
  • Pancreatic 10%
31
Q

Which genes are targeted in cancer?

A

Different classes of genes are targeted in cancer, which function in normal cell regulation

32
Q

Give examples of cancer susceptibility genes targeted in cancer

A

Growth promoting proto-oncogenes
- RET in MEN2

Growth inhibiting tumour suppressor genes
- RB1 in retinoblastoma

Genes involved in DNA damage repair
- BRCA1 and BRCA2 genes in breast/ovarian cancer

33
Q

What other mechanisms of oncogenesis are there?

A
  • Epigenetic mechanisms of oncogenesis

- Chromosomal aberrations

34
Q

What points should be covered when taking a family history?

A
  • 3 generation family history
  • Ask about consanguinity
  • Ethnic background
  • Types and ages of all cancers 🡪 specifically ask this
35
Q

Why is a family history not enough to diagnose?

A

Some individuals with a hereditary predisposition to cancer do not have a family history of cancer

36
Q

What should we be wary of when taking family history?

A

Look for multiple cancer diagnoses of cancers related to specific CPG in closely related individuals e.g. BRCA gene mutations increase risk of breast and ovarian cancer

Breast cancer affects 1 in 8 women across UK, very rare if <40

Unusual to have sporadic cancer at young age - red flag

37
Q

What is the effect of lynch syndrome?

A

Lynch syndrome caused by different set of mutations in cancer predisposition genes tends to cause bowel, ovarian, womb and gut cancers

38
Q

Why is it important to test the pathology of the cancer?

A

Certain pathological subtypes of cancer increase risk of high risk CPGs

39
Q

Name examples of high risk CPGs

A
  • High grade serous ovarian cancer: BRCA1/2
  • Medullary thyroid cancer: RET
  • Triple negative breast cancer: BRCA1/2
  • Type 2 papillary kidney cancer: FH
40
Q

Why is it significant to carry out molecular testing of cancer?

A

Tumour testing may identify genetic changes which indicate inherited risk

41
Q

How is molecular testing doublechecked?

A

Check with blood test e.g.

  • Immunohistochemistry of mismatch repair genes in Lynch syndrome
  • BRCA gene sequencing in ovarian cancer
42
Q

What causes syndromic effects in cancer?

A

There are High risk syndromic cancer genes as well which present with identifiable syndromic features

43
Q

What is trichilemomma?

A

Tricholemmoma is a benign tumour originating from the outer root sheath of the hair follicle

44
Q

What are the syndromic features of trichilemmomas?

A

present as well-defined, smooth, asymptomatic papules or verrucoid growths on the head / face

45
Q

What causes trichilemmomas?

A

Trichilemmoma strongly associated with P10 gene mutations causing cowden syndrome - increased risk of thyroid, breast and womb cancer: v rare

46
Q

What is the consequence of STK11 gene mutations?

A

STK11 gene mutations causes peutz-jeghers syndrome associated with an increased risk of breast cancer and bowel polyps

47
Q

Summarise how to assess a cancer risk

A
  1. Take a 3 generational family history
    - Ages, types of cancer, no. of affected relatives
    - Ethnic origin; higher rate of CPG in some popn.
  2. Consider cancer types in detail
    - ?increase chance of high risk (CPG)
  3. Look for rare syndromic features
    - can indicate high risk CPG
  4. Use National Genomic Test Directory Eligibility Criteria
    to decide if genetic testing is indicated
48
Q

Describe how you would manage a patient with a multifactorial riisk with <10% CPG chance ?

A

Multifactorial / polygenic risk: <10% chance of CPG or gene testing is negative

We would offer screening, prevention and early detection advice (SPED)

49
Q

What is chemoprevention?

A

Taking medicine to reduce cancer risk

50
Q

What drugs are available for breast cancer?

A

Breast cancer: Tamoxifen / selective estrogen reuptake modulator (SERM)

51
Q

What are the side effects of chemoprevention of breast cancer?

A

Reduce cancer risk but produce side effects - menopausal symptoms

52
Q

What drug is used to reduce risk of colorectal cancer?

A

Colorectal cancer: daily aspirin in multifactorial cancer reduces risk

53
Q

What considerations for the individual should be assessed before genetic testing?

A

Recurrence risks

Risks of other cancers

54
Q

What are the implications for relatives when genetic testing for CPGs?

A
  • How to share information
  • Concerns about children
  • Predictive testing

Family planning options (e.g. prenatal, PGD)

55
Q

What is diagnostic testing?

A

Diagnostic - to confirm whether a CPG has causes the cancer

56
Q

What is predictive testing?

A

Predictive testing - to identify if an unaffected person carries a CPG - insurance implications

57
Q

What are the possible genetic testing outcomes?

A

> no genetic variant identified
disease causing variant in CPG identified
variant of uncertain significance (VUS) identified

58
Q

What are the next steps for no genetic variant identified?

A

Screening and management on personal and family history

Referral for screening/further management only if indicated on above assessment

Reassuring for patient but reiterate participation in population screening programmes

59
Q

How do we follow an identified CPG causing disease?

A

Screening and management tailored to specific CPG

Should be reviewed by NHS clinical genetics service

60
Q

What do we do if a VUS is identified?

A

Benign until proven guilty

Referral for screening/further management only if indicated on above assessment

May be anxiety provoking for patients

Need to understand how common genetic variant is and that most VUS are benign

Clinical Genetics (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions