week 7

Question 1

Driver mutations involved in cancer?

Answer 1

1) proto-oncogene (becoming oncogeene)
2) Tumour supressor gene

Question 2

proto-oncogens when mutated become?

Answer 2

Oncogeenes

Question 3

Burkitt Lymphoma mutation

Answer 3

dysregulated MYC expression on chromosome 8 and 14

* Excessive production of MYC proetein

Question 4

Mutations involved in ‘Philadelphia’ chromosome in Chronic Myeloid Leukaemia (CML)

Answer 4

1) BCR –> chromosome 22
2) ALB1 -> chromosome 9

Question 5

The translocation break point in BCR and ALB1 genes [involved in ‘Philadelphia’ chromosome in Chronic Myeloid Leukaemia(CML)] are located in gene ——–, which result in —-, ——- gene

Answer 5

The translocation break point in BCR and ALB1 genes [involved in ‘Philadelphia’ chromosome in Chronic Myeloid Leukaemia(CML)] are located in gene introns, which result in novel, chimeric gene

* chimeric gene –> BCR-ALB1 (increased gene activity)

Question 6

[one/two] allele(s) of the proto-oncogene may need to be altered for tumour formation to be initiated

Answer 6

Only one

Question 7

[1/2]alleles in Tumour supressor genes need to lose their function for tumour to develop

Answer 7

Both alleles

Question 8

Inherited TSG loss-of-fx mutations increase significatnly the risk of cancer. how many hits are requried for cancer to develop?

Answer 8

Only second hit required
(these type of cancers are normally aquired at a younger age, may devlop in multiple, distinct sites. And may be bilateral like retinoblastoma)

Question 9

Gene involved in Retinoblastoma?

Answer 9

RB1 gene

Question 10

If inherited TSG loss of function is biallelic, phenotype is [milder/more sever]

Answer 10

More severe

Question 11

Which gene cause Breast cancer in males

Answer 11

BRCA2
(Also includes prostatic cancer)

BRCA1 has higher risks in causing breast cancer, ovarien cancer etc in F

Question 12

Surveillance management following diagnosis (BRCA1/2)

Answer 12

• SOS: Transvaginal ultrasound and serum CA-125
• MRI/ Mammograms (start at 30, or earlier for MRI)
• clinical surveillance (breast)

Question 13

Faconi anaemia MoI and Mutation

Answer 13

MoI: AR
Mutation: BRCA2 ( 18 AR loci)

Question 14

CM of Fanconi anaemia

Answer 14

1) microcephaly,
2) limb abnormalities (hypoplastic thumb/ radius),
3) abnormal skin pigmentation (hypo/hyper pigmentation),
4) ophthalmic,
5) genitourinary
6) Bone marrow failure with pancytopaenia
7) Increased risk for malignancy–Acute myeloid leukaemia, solid tumours

• Pancytopaenia –> deficiency of all three cellular components of the blood (red cells, white cells, and platelets)

Question 15

Xerodema Pigmentosum MoI and Mutation

Answer 15

MoI: AR
mutation: XP gene

Question 16

CM of Xeroderma Pigmentosum

Answer 16

1) Sun sensitivity (severe sunburn, blisters, freckling)
2) Ocular involvement (inflammation, keratitis, eyelid abnormalities)
3) Increase in skin cancer risk (sunlight-induced)
4) Neurological manifestations

Question 17

Ataxia Telangiectasia MoI+ mutation

Answer 17

MoI: AR
Mutation: ATM gene

Question 18

CM of Ataxia Telangiectasia

Answer 18

1) Cerebellar ataxia (1-4 years)
2) Telangiectasia
3) Immunodeficiency
4) Sensitivity to ionising radiation
5) Increased risk of malignancy (leukaemia and lymphoma)

Question 19

Bloom Syndrome MoI and mutation

Answer 19

MoI: AR
Mutation: BLM

Question 20

CM of Bloom Syndrome

Answer 20

Severe pre and postnatal growth retardation, sunsensitivity, increased cancer risk (wide variety)

Question 21

Nijmegen breakage syndrome MoI and mutation

Answer 21

MoI: AR
mutation: NBS

Question 22

CM of Nijmegen breakage syndrome

Answer 22

Progressive microcephaly, growth retardation, recurrent chest infections, increased risk of malignancy (lymphomas and solid tumours)

Question 23

***

Lynch Syndrome MoI and mutation

* CANCER predisposition syndrome

Answer 23

MoI: AD
Mutation: MLH1, MSH2 (EPCAM*), MSH6, PMS2

* mutations in mismatch repaire genes

Question 24

CF of Lynch Syndrome

Answer 24

1) Large number of polyps
2) Adenomatous polyps do develop in Lynch but they are in small numbers

Question 25

# *** Colorectal cancer is linked with a number of syndromes featuring **------**

Answer 25

Colorectal cancer is linked with a number of syndromes featuring **multiple polyps**

Question 26

# *** Clinical management of Lynch syndrome (in individuals not diagnosed with cancer)

Answer 26

* Primary prevention: --> Prophylactic removal of uterus and ovaries * Surveillance -> **Colonoscopy (from 20-25, every 1-2 years) and removal of adenomas is highly effective** - Upper GI endoscopy and urinalysis

Question 27

Peutz-Jegherssyndrome MoI + Mutation

Answer 27

MoI: AD Mutation: STK11 tumour supressor gene

Question 28

CF of Peutz-Jeghers syndrome

Answer 28

Characterised by: 1) Gastrointestinal polyps (**hamartomas**) 2) **Mucocutaneous pigmentation** 3) **Cancer predisposition**: includes Colorectal (39%), Breast (up to 54%), Gastric (29%), Small bowel (13%), Pancreas (up to 36%), ovarian tumours (21%, mainly sex cord)

Question 29

Familial adenomatous polyposis (FAP) MoI and mutation

Answer 29

MoI: AD mutation: APC gene tumour supressor gene

Question 30

CM of Familial adenomatous polyposis (FAP)

Answer 30

1) **Hundreds to thousands of adenomatous colonic polyps** 2) By age of **35** most individuals with FAP have polyps 3) **Colorectal cancer develops if colectomy is not performed **

Question 31

Extracolonic mifestations in FAP

Answer 31

1) polyps of duodenum/ stomach 2) desmoid tumours 3) Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) 4) associated cancers (thyroid, small bowel, hepatoblastoma)