Cancer genetics

Question 1

What are the key clinical features of MEN -1

Answer 1

3 Ps
Parathyroid adenoma - 90%
Pituitary Ademona - 15%
Pancreatic islet cells/ GI ademonas - 65%
Gene = MENIN
AUTOSOMAL DOMINANT

Question 2

What are the key clinical features of MEN 2a

Answer 2

Medullary thyroid cancer 
Pheochromocytoma
Parathyroid Hyperplasia
Gene = RET
Autosomal dominant

Question 3

What are the key clinical features of MEN 2b

Answer 3

Medullary thyroid cancer
Pheochromocytoma
Marfanoid features
Gene = RET
Autosomal dominant

Question 4

What are the BRCA genes? What is their role?

Answer 4

Tumour suppressor genes. Code for double stranded DNA repair

Question 5

BRCA 1

Answer 5

<40yrs
Triple negative breast cancer - 57% RR
High grade serous ovarian cancer - 40% RR

Question 6

BRCA 2

Answer 6

<40yrs
More likely ER and PR positive - 49% RR
Male breast cancer - 5-6% RR
Ovarian cancer 18% RR
Pancreatic cancer <5% RR

Question 7

Risk reducing strategies for BRCA?

Answer 7

Prophylactic Bilat mastectomy and BSO
Yearly mammogram from 30yrs
BSO at 40yrs

Question 8

Li Fraumeni Syndrome

Answer 8

Rare Tp53 mutation
SBLA - Sarcoma, Breast, Leukaemia and Adrenal gland cancers
Breast = HER2 positive
Young age of cancer <30yrs, 95% have cancer by 70yrs

Question 9

Cowden Syndrome

Answer 9

Very Rare PTEN mutation 
Breast cancer - 85% lifetime risk
Endometrial cancer
Follicular thyroid cancer
Large head
Lhermitte Duclos

Question 10

FAP

Answer 10

Mutation in the APC tumour suppressor gene.
AD inheritence with 25% de novo mutations
Multiple adenmatous polyps –> cancer
Mean age of diagnosis 40yrs
Also get CHRPE, desmoid tumors

Question 11

Management of FAP

Answer 11

Prophylactic colectomy at 20yrs

Colonscopy from 10yrs

Question 12

If a patient presents with multiple polyps and cancer and APC gene is negative what is the disorder?

Answer 12

MutYH
Cancer by 45yrs
No desmoids
Autosomal recessive

Question 13

Peutz Jegher syndrome

Answer 13

Very rare - STK11 gene mutation 
Autosomal dominant
Increased risk of breast and bowel cancer
Haemartatous polyposis
lip, buccal, palm pigmentation
Intrasussception/volvulus in adults

Question 14

What kind of mutation results in lynch syndrome

Answer 14

Mismatch repair gene mutations - MSH2, MLH1, MSH 6, PMS2
Autosomal dominant
No BRAF V600E mutations

Question 15

What are the diagnostic criteria for Lynch syndrome

Answer 15

Amsterdam criteria:
3 or more relative with colorectal cancer
2 or more generations
1 or more <50yrs
Not FAP

Question 16

What cancers are associated with lynch syndrome?

Answer 16

Bowel cancer -70-80% RR
Endometrial cancer 40-50% RR
Gastric cancer 5-15%
Ovarian up to 10%
Urothelial, brain and small bowel 1-5%

Question 17

Risk reduction strategies for lynch syndrome?

Answer 17

Colorectal cancer = annual colonscopy from 25yrs ?aspirin
Endometrial = hystectomy at 40yrs
Ovarina cancer = BSOH at 40yrs
Gastric cancer = 2yrly gastroscopy from 30yrs

Question 18

Neurofibromatosis Type 1 clinical features

Answer 18

Gene = Neurofibromin 1 AD 50% de novo
>6 cafe au lait spots
>2 neurofibromas
Axillary freckling
Lisch nodules on iris
Optic gliomas
Tibial psuedoarthosis

Question 19

Neurofibromatosis Type 2 clinical features

Answer 19

Gene = Merlin AD 50% de novo
Bilateral accoustic schwannoma
Other intracranial and spinal tumours
Polyneuropathy
Cataracts
Cutaneous tumours and plaques

Question 20

Von Hippel Lindau Disease

Answer 20

Gene = VHL gene
Renal clear cell cancer
Pheochromocytoma
CNS haemangioblastoma