Diseases

Question 1

Multiple Endocrine Neoplasm 2 (Men2)

Answer 1

AD-Mutation of Ret (receptor tyrosine kinase), affects greater then 2 endocrine organs,
loss of function Hirschprung

Question 2

Heriditory Papillary Renal Carcinoma

Answer 2

AD-mutation of Met (HGFR) involved in embryonic development, wound healing

Question 3

Burkitt Lymphoma

Answer 3

Sporadic
Endemic- Eppstein Barr Virus, presents in jaw
non-endemic- 8:14 translocation putting Myc under control of a strong Ig promoter increased proliferation
HIV

Question 4

Follicular Lymphoma

Answer 4

Sporadic-Translocation 14:18 Bcl2 is placed under control of a strong Ig promoter. decrease apoptosis
follicular lymphoma of the B-cells

Question 5

Chronic Myelogenous Leukaemia (CML)

Answer 5

Sporadic- Translocation(9:22) Philadelphia results in constitutively active BCR-ABL fusion protein which actives Tyr Kinase activity promoting cell growth and inhibiting apoptosis.
Chronic and Blast/crisis phase (due to chromosomal rearrangements)
Treated with Imatinab/Glevec which binds and block RTK activity
presents with splenomegaly

Question 6

Acute promyelocytic leukaemia( APL)

Answer 6

Sporadic- Translocation 15:17 Fusion PML-RARalpha. Retonic acid receptor is converted to a repressor turning off genes for myeloid differentiation

Question 7

Ewing Sarcoma

Answer 7

Sporadic- Translocation 11:22 EWS-FLI1 (TF) fusion presents as tumors on bone and soft tissue

Question 8

Retinoblastoma

Answer 8

inherited mutation of the RB1 phospoprotein which normally binds and represses E2F to inhibit cell proliferation.
40% inherited resulting in early onset (<1 year) , multiple bilateral tumors. 400x risk of developing other cancers
60% sporadic results in later onset single tumor

Question 9

Li-Fraumeni Syndrome

Answer 9

inherited p53 mutation which is a TF involved in DNA regulation and repair.
Results in highly variable phenotype

Question 10

Neurofibromatosis type I (NF1)

Answer 10

inherited Mutation of NF1 a Ras-Gap which shuts off Map Kinase signalling. A mutation results in constituitvely active Ras signaling= tumour grpwth
50% hereditary, 50% sporadic
presents as a highly variable neurocutaneous syndrome with cafe au lait and lisch nodules

Question 11

Familial Breast Cancer

Answer 11

inherited mutation of BRCA1, BRCA2 which are involved in dsDNA breakage response and repair
results in breast, ovarian, and prostate cancer

Question 12

Familial Adenomatous Polyposis (FAP)

Answer 12

inherited mutation of APC which normally binds, inhibits, and degrades B catenin preventing Myc activation
Wnt >Frizzled > Dishevelled can inhibit the APC complex promoting myc activation = cell proliferation
characterized by the formation of colon polyps

Question 13

Hereditary Non-polyposis Colorectal Cancer

Answer 13

mutation in DNA repair gene such as MLH1, MSH2, or PMS2 resulting from pt mutations or MSI in RER+ phenotypes
TGFB receptor 2 is frequently mutated in 70% of HNPCC as a result of frameshift mutation. TGFBR2 is a serine kinase which inhibits the E2F complex formation

Question 14

Sporadic Colorectal Cancer

Answer 14

70% loss of APC or 30% mutation in B catenin
70% loss of DCC
Smad4 or mismatch repair genes also frequently mutated
70% loss of TGFB2,

Question 15

Wilm’s tumor

Answer 15

Loss of WT-1 which is involved in renal development,

Paediatric kidney tumor

Question 16

Xeroderma Pigmentosum

Answer 16

AR Defect in nucleotide excision repair particularly excision endonuclease defiency
Greatly increased risk of pyrimidine dimers resulting from UV exposure = increased risk of skin cancer

Question 17

Ataxia Telegiectasia

Answer 17

AR Loss of ATM which initiates DNA repair through activation of p53 resulting in cell checkpoint failure
multi-system syndrome presents with telangiectasia, ataxia, immunodefiency

Question 18

Bloom Syndrome

Answer 18

AR Mutation of BLM = DNA helicase resulting in chromosomal instability due to excessive sister chromatid exchange (increased cancer risk)
high frequency of chromosome breaks and rearrangements
Immunodefiency

Question 19

Werner Syndrome

Answer 19

AR Mutation of WRN which is a helicase/ endonuclease involved in DNA unwinding and trimming of broken ends
Premature aging resulting from shortened telomeres and impaired DNA repair

Question 20

Faconi Anaemia

Answer 20

AR mutation of the FA genes which are involved in DNA repair resulting in chromomal breakage
presents with pancytopenia, upper skeletal limb deformities
increased risk of AML

Question 21

Human Papilloma Virus

Answer 21

Viral proteins E6,E7 bind and inhibit RB and p53 allowing excessive proliferation
cervical cancer

Question 22

Dyskeratosis Congenita

Answer 22

1 mutated telomerase allele results in prematurely shortening telomeres. Malignancy results form chromosomal instability
progressive bone marrow failure results in pancytopenia and immunosupression

Question 23

von Hippel-Landau Syndrome

Answer 23

AD 80% inherited mutation of the pVHL which is a uquititin ligase that binds and degrades HIF1 in the presence of oxygen. =excessive angiogenesis
presents with hemangioblastomas (bv tumours) of the CNS and retina

Question 24

von Willebrand Disease

Answer 24

inherited autosomal disorder resulting in defective platelet adhesion.
highly variable type and severity

Question 25

Factor V Leiden

Answer 25

A point mutation in Factor V replaces Arg with Gln making it resistant to APC.
This increases the risk of deep vein thrombosis
Found in Europeans

Question 26

Hemophilia A

Answer 26

X linked deficiency of Factor 8. Inversion results in most severe form

Question 27

Hemophilia B

Answer 27

mutation of Factor 9