Germline and Somatic Mutations

Question 1

Germline vs somatic mutation

Answer 1

Germline: inherited variation in germ cells (transmitted to offspring)
Somatic: acquired alteration of DNA sequence

Question 2

What is the most common risk factor for cancer?

Answer 2

Age

Question 3

3 clues in a personal history that there is a hereditary cancer present

Answer 3

Early age of onset
Multiple primary cancers
Rare cancer types

Question 4

4 clues in a family history that there is a hereditary cancer present

Answer 4

Same cancer in 2 or more relatives
Multiple generations affected
Same or related cancer types
Early age of onset of family members

Question 5

What type of inheritance is usually associated with hereditary cancers

Answer 5

Autosomal dominance

Question 6

3 conditions to be met for cancer genetic testing to be offered

Answer 6

Individual or family history suggestive of cancer susceptibility
Test can be adequately interpreted
Results will aid diagnosis or influence management of the patient/family members

Question 7

BRCA1/2 genes are associated with what cancer syndrome?

Answer 7

Hereditary breast and ovarian cancer syndrome

Question 8

Benefits of oncologist-led genetic testing

Answer 8

Improved efficiency (reduced wait times)
More effective working relationships with oncology team
Positive feedback from patients

Question 9

4 reasons to get a hereditary cancer diagnosis

Answer 9

May alter treatment
May help patient decide on risk-reducing strategies to manage risk of future cancer
May help prevent or detect cancer early in a family member
Family members can be tested to determine cancer risk

Question 10

3 ethical considerations of hereditary cancer testing

Answer 10

Psychological implications
Genetic discrimination
Disclosure of genetic results to relatives (duty to report vs confidentiality)

Question 11

5 places to sequence the genome

Answer 11

Site specific
Single gene
Gene panel
Whole exome
Whole genome

Question 12

Sanger sequencing

Answer 12

Based on selective incorporation of chain-terminating dideoxynucleotides
Used for smaller scale sequencing and validation of next gen sequencing

Question 13

3 main steps of next generation sequencing

Answer 13

1. Library (break up entire genome)
2. Sequencing
3. Data analysis

Question 14

3 pros and 1 con of single gene sequencing

Answer 14

Pros: targeted assessment, fewer variants of uncertain significance, accurate
Con: time consuming

Question 15

3 pros and 1 con to using a multi gene panel

Answer 15

Pros: increases likelihood of detecting a mutation, unexpected diagnosis impacting management, time and cost efficient
Con: Increases numbers of VUS

Question 16

2 pros and 2 cons to whole genome sequenceing

Answer 16

Pro: comprehensive assessment, can evaluate structural changes/copy number changes/mutational signatures
Cons: high number of VUS, expensive