Clinical Genetics

Question 1

what percentage of breast cancers are familial or heritable?

Answer 1

5-25%

Question 2

what percentage of ovarian cancers are familial or heritable?

Answer 2

5-10%

Question 3

define a germline mutation, and its consequence in offpsring

Answer 3

mutation in sperm/egg gene - will be present in all cells of offspring, can cause familial cancers

Question 4

define a somatic mutation, and its consequence in offspring

Answer 4

mutation in a developed cell - will only be present in one cell, not heritable

Question 5

which main types of genes involved in the cell cycle are involved in cancer development? where do they act in the cell cycle and how?

Answer 5

oncogenes - promote cell growth during G1 phase
tumor suppressor genes - halt DNA synthesis until cell is ready - act before S phase
DNA repair genes - act after S phase and before G2 phase, check DNA synthesis is correct

Question 6

many familial cancers are caused by problems in which types of genes involved in the cell cycle?

Answer 6

DNA repair genes

Question 7

explain the two-hit theory in cancer development

Answer 7

• an insult causing loss/damage to one allele will cause predisposition to cancer
• a second insult to the other copy of that allele will cause cancer development

Question 8

familial adenomatous polyposis is caused by loss of which gene? (name and type of gene)

Answer 8

APC - a tumor suppressor gene

Question 9

retinoblastoma is caused by damage to which gene (name and type of gene)

Answer 9

retinoblastoma gene - a tumor suppressor gene

Question 10

what is Lynch syndrome also known as?

Answer 10

it is hereditary non-polyposis colorectal cancer

Question 11

mutation of which genes leads to Lynch syndrome?

Answer 11

mutation in DNA mismatch repair genes

Question 12

what cancers are prevalent in Lynch syndrome?

Answer 12

colorectal
ovarian
endometrial
stomach
biliary tract

Question 13

which genders are linked to which genetic mutation for breast cancer? what other cancers may occur?

Answer 13

women - BRCA1; breast and ovarian

males - BRCA2: breast and prostate

Question 14

what is the unusual medication which seems to be effective in reducing colorectal cancer risk in patients with Lynch syndrome?

Answer 14

daily aspirin for 2+ years

Question 15

name the characteristic features of autosomal dominant disorders

Answer 15

• no skipped generations
• 50% chance for offspring to carry disorder
• equal transmission by men and women

Question 16

when is a patient at high risk of having a hereditary cancer syndrome?

Answer 16

• multiple primary tumours
• pattern of rare/specific tumours
• 2+ cancers in close members on same side of family
• young age at onset
• evidence of autosomal dominant transmission

Question 17

how is hereditary cancer incidence kept to a minimum?

Answer 17

• early and regular screening
• prophylactic surgery
• genetic testing

Question 18

name two types of genetic testing that can be done to test for Lynch syndrome

Answer 18

• immunohistochemistry (IHC)

- mini satellite instability (MSI)

Question 19

what causes Li-Fraumeni syndrome?

Answer 19

mutation in P53, a tumor suppressor gene

Question 20

what cancers are associated with Li-Fraumeni syndrome?

Answer 20

SBLA - sarcoma, breast, leukaemia, adrenal gland

Question 21

what modes of inheritance are possible in multi-system genetic diseases?

Answer 21

• chromosomal
• single gene
• multifactorial

Question 22

in clinical genetics, why do some genetic conditions affect more than one system?

Answer 22

• because various genes are involved (chromosomal abnormalities)
• because the faulty gene is present in many types of tissues
• because the faulty gene is specific to one tissue, but that tissue is found in many systems

Question 23

in clinical genetics, what are some problems associated with diagnosing genetic multi-system diseases?

Answer 23

• they can present differently within the same families
• they can present to many different specialties
• they can be difficult to identify from a family history

Question 24

what mode of inheritance do tuberous sclerosis, neurofibromatosis type 1 and myotonic dystrophy present?

Answer 24

autosomal dominant inheritance

Question 25

what is the common symptom triad of tuberous sclerosis?

Answer 25

epilepsy, skin lesions and learning difficulties