20.06.18 Genetics of lymphoma Flashcards
1
Q
What is lymphoma
A
- Malignant lymphocytes (B and T cells) that accumulate in lymph nodes to form tumours
- 5th most common cancer in UK
- Uncontrolled proliferation of lymphocytes
2
Q
What are the phases of disease in lymphoma
A
- Leukemic phase: lymphocytes spill over into blood
- Extranodal disease: lymphocytes infiltrate organs (mostly spleen) outside of lymphoid tissue
3
Q
Review of Hodgkin’s lymphoma
A
- Diagnosis is by finding multinucleated Reed–Sternberg cells (RS cells) in lymph node
- RS cells are of B-lymphoid lineage
- EBV (Epstein Barr Virus) genome in 50% cases
- Peak incidence in young adults. 2:1 male predominance.
- Phenotypic characteristics: painless enlargement of superficial lymph nodes. Weight loss, fever, sweating.
- Diagnosed by histological examination of excised lymph node. Staged to determine course of treatment (radiotherapy, chemotherapy or both).
- Good prognosis (85% survival rate)
4
Q
Review of non-Hodgkin’s lymphoma
A
- Clonal lymphoid tumour
- 85% is B-cell lymphoma, 15% is T cell lymphoma
- Presentation more variable can be low grade (later presentation slow progression) or high grade (early presentation, rapid progression).
5
Q
What are the characteristic chromosomal abnormalities seen in B cell lymphomas
A
Reciprocal translocations involving immunoglobulin genes.
6
Q
Review of Burkitt’s lymphoma
A
- 1/3rd of all childhood lymphoma, 3-4% of adult lymphoma
- Acute, aggressive, high grade
- Frequently associated with immunodeficiency
- t(8;14)(q24;q32) is present in ~85% of cases.
- MYC and IGH (immunoglobin heavy chain)
7
Q
Review of Follicular lymphoma
A
- Peak incidence in 5th and 6th decade.
- 20% of adult lymphomas
- 80% carry (t14;18)(q32;q21)
- BCL2 and IGH (causes overexpression of BCL2, preventing cells from apoptosing)
- Treated with rituximab (anti-CD20 antibody, found on B cells)
8
Q
Review of Mantle cell lymphoma (MCL)
A
- 5% of non-Hodgkin lymphoma
- Male predominance and median age is 65 yrs
- t(11;14)(q13;q32) in 95% cases
- CCND1 (or BCL1) and IGH. CCND1 accelerates passage through G1 phase of cell cycle causing them to divide before they mature.
9
Q
Review of Diffuse large B cell lymphoma (DLBCL)
A
- High grade, acute, aggressive
- Large B cell cells with big nuclei
- t(14;18)(q32;q21) IGH/BCL2 rearrangement in ~50% cases
- t(3;14)(q27;q32) BCL6/IGH rearrangements in 20-35% of cases
10
Q
Review of Marginal Zone lymphoma (MZL)
A
- 10% of non-Hodgkin lymphoma
- Indolent clinical course but could transform to high grade.
- 3 subtypes: MALT (mucosa associated lymphoid tissue), Splenic and nodal.
- Rituximab therapy, Helicobacter pylori eradication (in MALT form).
- t(11;18)(q21;q21) BIRC3-MALT1 fusion in 20-50% of MALT.
- Total/partial trisomy 3 in 30-50% of splenic MZL
11
Q
Review of Anaplastic large cell lymphoma (ALCL) ALK positive
A
- T cell lymphoma
- 10-20% of childhood lymphomas
- Tanslocations involve ALK (2p23)
- t(2;5)(p23;q35) in 85% cases
- Prognosis better than ALK -ve
12
Q
Testing strategies
A
- Karyotyping: recommended where fresh tissue is available. Clarifies FISH results. Detects complexity (common in lymphomas). However, culture is labor intensive, time consuming, high failure rate and expensive.
- FISH: loci specific, rapid, robust and cheap. Could miss complexity of karyotypes.
- ArrayCGH: Does not require dividing cells, genome wide. Can only detect gain or loss, not balanced aberrations.
- SNP array: Can detect regions of acquired copy number neutral LOH, requires paired germline and tumour samples. Cannot detect balanced aberrations.
- Microarray gene expression profiling: whole transcriptome or targeted. Not available in diagnostic setting.
- PCR: used for clonality analysis, can detect recurrent translocations (complicated by diversity of breakpoints), sensitive. RT-PCR not widely used as minority of rearrangements produce fusion mRNA transcripts
- Immunohistochemistry: could cause aberrant gene expression. Monoclonal antibodies against protein products could be used to detect aberrant expression.
