Extra reading Flashcards
(35 cards)
What is the proper notation for the Philadelphia chromosome?
t(9;22)(q34;q11.2)
What gene fusion is seen in follicular lymphoma?
- t(14;18)(q32;q21)
- IGH promoter and BLC2 fusion
What gene fusion is seen in APL?
- Acute promyelocytic leukaemia
- t(15;17)(q24;q21)
- PML-RARA
What is the MLL gene? (4)
- MLL = mixed lineage leukaemia
- MLL has over 40 gene fusion partners
- E.g. MLL-AF4 and MLL-AF9 most common
- 11q23 disturbance = poor prognosis
What is the location of MLL gene?
11q23
What fusion gene is seen in prostate cancer?
TMPRSS2-ERG results in generation of a neoplastic phenotype
What is the total number of gene fusions identified?
Nearly 10 000
What are TIGFs?
- Transcription-induced gene fusions
- Chimeric transcripts beginning at the promoter region of upstream gene and ending at the termination region of the downstream gene
- E.g. Hodgkin’s lymphoma CD205-DCL1 fusion protein
What happens to MYC in Burkitt lymphoma?
Multiple fusions have been identified involving chromosome 8q24 fusion with immunoglobulin promoter regions (MYC location) = MYC overexpression = proliferation
What are the 3 oncogenic impacts of chromosomal rearrangement?
- Fusion protein formation
- Gene fusion to highly expressed promoter
- Gene truncations resulting in activation of tumour suppressors
What is the targeted therapy for APL?
- ATRA plus arsenic trioxide
- Causes terminal differentiation of APL cells
- 90% achieve long term remission
What are the risks associated with APL?
- High pre-treatment mortality rate usually caused by cerebral haemorrhage
- DIC = disseminated intravascular coagulation, causes abnormal clotting
What are the features of PML and RARA? (2)
- RARA is a transcription factor which is activated by retinoids and acts as a ligand-dependent differentiating factor of normal myeloid haematopoietic cells
- PML is a tumour suppressor protein organised into nuclear bodies (PML-NBs)
What is caused by PML-RARA fusion?
- Alters the structure of the PML-NBs, resulting in nuclear microspeckles
- Fusion protein has a dominant negative and gain of function effect
- PML-RARA represses genes involved in myeloid differentiation
What further abnormalities are seen in APL?
- 1-2% APL patients have novel translocations other than t(15;17) involving RARA
- Almost half of APL patients have further alterations such as del7q and trisomy 8 (most prevalent)
What is CPM?
Confined placental mosaicism
What is the most common viable aneuploidy?
Trisomy 21
What is the most common human aneuploidy?
- Trisomy 16 (observed in pregnancies)
- Estimated to occur in 1-1.5% of all pregnancies
- Trisomic rescue in up to 10% of T16 pregnancies
What abnormality causes Emanuel syndrome?
- t(11;22) - one of the most common non-Robertsonian translocations in humans
- 3:1 meiotic malsegregation of derivative 22 results in partial trisomy for Ch22
What characterises the breakpoints for t(11;22) translocation?
- AT-rich palindromic repeats (PATRRs), susceptible to DSBs which are then
What disease is caused by maternal UPD 14?
Temple syndrome
What are complex abnormalities?
AML patients with 3 or more acquired chromosomal abnormalities other than 15;17, 8;21, inv16 (favourable) can be referred to as AML with complex karyotype
What is an example of epigenetic modifications in cancer?
- EN1 (regulates growth and proliferation) methylation observed to be elevated by up to 60% in human salivary gland adenoid cystic carcinoma
- EN1 and SCTR methylation increased in colorectal and prostate cancers
What is FLT3-ITD?
- Example of a poor prognostic marker in AML
- FLT3 is a tyrosine kinase, mutation leaves it constitutively active = proliferation
- ITD = internal tandem duplication
