Cancer Genetics AB

Question 1

Gastric cancer - what are the genetic associations?

Answer 1

BRCA2
HNPCC
Peutz-Jegher
Familial Diffuse Gastric Cancer (CHD1 or e-cadherin gene)

Question 2

Familial Diffuse Gastric Cancer - who does it affect and what is the incidence of cancer?

Answer 2

Maoris in NZ
Newr 100% incidence of gastric cancer
Also lobular breast cancer
Remove stomachs when they get to adulthood

Question 3

Gastric cancer - what are the molecular subtypes?

Answer 3

CIN
EBV associated
MSI
GS - gastric subtype; correlates with diffuse gastric cancer

Question 4

Familial adenomatous polyposis - what is the underlying genetic abnormality?

Answer 4

Autosomal dominant

Mutation in APC gene

Question 5

Lynch syndrome - what are the underlying genetic mutations?

Answer 5

Autosomal dominant
Germline mutation leading to mismatch repair

Mutations in MLH1, MSH2, MLH3, PSM - can be identified on ICH of the tumour tissue

Question 6

Lynch syndrome - which cancers are associated with this syndrome?

Answer 6

Colon
Endometrial
Ovarian
Stomach 
Hepatobiliary
Urinary tract
Brain

Question 7

What is the recommended screening/management of FAP?

Answer 7

Total colectomy with ileorectal anastomosis
Sigmoidoscopy from age 12-15
Duodenal screening fro age 25 or at time of colectomy

Question 8

What is the recommended screening for HNPCC?

Answer 8

Colonoscopy 1-2 yearly from age 25 or 5 years younger than familial case

? Screen for extracolonic tumours

Question 9

Breast cancer - what are the genetic associations?

Answer 9

5-10% of breast cancers are gene related

BRCA 1/2
PTEN
p53
ATM
MLH1
MSH2

Question 10

What is the mutation in Li-Fraumeni syndrome?

Answer 10

p53 - Ch 17

Autosomal dominant

Question 11

What is the mutation in Cowden syndrome?

Answer 11

PTEN - Ch 10

Question 12

What cancers are seen in Cowden syndrome?

Answer 12

Breast - 25-50%
Ovarian - 1%
Thyroid
Endometrial
Genitourinary

Question 13

What cancers are seen in Li-Fraumeni syndrome?

Answer 13

Breast - >90%
Soft tissue sarcoma
Brain tumours
Adrenocortical cancer
Leukaemia
Colon

Question 14

What is the genetic mutation in Peutz-Jeghers syndrome?

Answer 14

STK11/LKB1

Question 15

What cancers are seen in Peutz-Jeghers?

Answer 15

Breast cancer - 50%
Sex cord tumours
Small intestine
Colorectal Urterine
Testicular

Question 16

What is the mutation seen in hereditary diffuse gastric cancer?

Answer 16

CDH1

Question 17

What are the mutations seen in HNPCC/Lynch syndrome?

Answer 17

MLH1
MSH2
MSH6
PMS1
PMS2

Question 18

Does BRCA1 or BRCA2 confer a higher risk for developing prostate cancer?

Answer 18

BRCA2 (RR 4+)

Question 19

What are the histologic features of BRCA1 breast cancer?

Answer 19

High grade
Hormone receptor negative 75%
Pushing borders 
Less DCIS
Medullary histology
Stains positive for basal keratin

Question 20

Which chromosomes are BRCA1 and BRCA2 located on?

Answer 20

BRCA1 = Ch 17q
BRCA2 = Ch 13q

Question 21

When do you perform genetic testing in breast and ovarian cancer where there is NO family history?

Answer 21

Breast cancer

Question 22

Which familial cancer is PLAB2 similar to?

Answer 22

BRCA2

Question 23

How effective is chemoprevention (e.g. Tamoxifen) at primary prevention of breast cancer?

Answer 23

Reduces risk of hormone positive breast cancer by 30-40%

Not associated with proven survival benefit

Younger high risk women benefit most

Question 24

What is the penetrance of Li Fraumeni syndrome by age 60?

Answer 24

90%

Question 25

What is Gardner syndrome?

Answer 25

FAP + extra-intestinal features (osteomas, desmoid tumours, epidermoid cysts)

Question 26

What is Turcot syndrome?

Answer 26

Familial colon cancer + primary brain tumour Medulloblastoma in FAP GBM in Lynch

Question 27

What does MYH polyposis resemble?

Answer 27

Attenuated FAP

Question 28

What is the mode of inheritance of MYH polyposis?

Answer 28

Autosomal recessive

Question 29

What are the common genetic abnormalities in serrated polyps?

Answer 29

Widespread DNA methylation and frequent BRAF +

Question 30

What is the genetic abnormality associated with familial paraganglioma syndrome?

Answer 30

Autosomal dominant, variable penetrance Mainly SDHB, SDHD Testing: screen with IHC looking for absent SDH protein

Question 31

What are the genetic associations with phaeochromocytoma?

Answer 31

``` vHL MEN2 SDH mutations MH1 RET NF1 ```

Question 32

What are the findings in Birt-Hogg-Dube syndrome?

Answer 32

Bilateral multifocal kidney cancer (usually chromophobe) Skin signs (fibrofolliculoma)

Question 33

What is the mode of inheritance of von Hippel Lindau?

Answer 33

Autosomal dominant Germline mutation of VHL gene - Ch 3p

Question 34

What are the typical abnormalities in von Hippel Lindau syndrome?

Answer 34

Cerebellar or spinal haemangioblastomas Retinal angiomas Clear cell renal cancer Phaeochromocytoma

Question 35

What tumours occur in NF1?

Answer 35

10% get cancer Optic nerve gliomas and other astrocytomas Childhood leukaemias Phaeochromocytoma Other sarcomas (GIST)

Question 36

What are the risks associated with P16 mutations?

Answer 36

High risk of melanoma | Some increased risk of pancreatic cancer

Question 37

What on earth is BAP?

Answer 37

BAP = BRCA1 associated protein Associated: melanomas, mesothelioma, lung adenocarcinoma, meningioma

Question 38

What are POLD1 and POLE mutations associated with?

Answer 38

Polyposis, CRC POLD1 also endometrial cancer Lynch syndrome-like families without mutation