Translocations, amplifications and epigenetic changes in cancer !
- Topic
Besides point mutations, cancers swap chromosome pieces, copy genes many times and silence genes without changing their sequence.
Updated 2026-11-01
What it is
Many tumours are driven by large-scale changes: balanced translocations that create fusion proteins or move an oncogene under a strong promoter, gene amplifications that multiply an oncogene, and epigenetic changes such as promoter hypermethylation that silence tumour suppressors. Translocations are especially typical of leukaemias, lymphomas and sarcomas, and they are diagnostic tools detected by karyotype, FISH or PCR.
Key facts
- Translocations involving immunoglobulin or T-cell receptor genes arise from errors of the normal recombination machinery of lymphocytes.
- Amplified genes appear as double minutes or homogeneously staining regions on a karyotype.
- Cancer genomes show global DNA hypomethylation together with focal hypermethylation of tumour suppressor promoters.
- Mutations in chromatin regulators (for example EZH2, ARID1A) are common in many cancers.
- Epigenetic marks are reversible, which makes them drug targets (hypomethylating agents in myelodysplastic syndromes).
Translocations to know
| Translocation | Genes involved | Effect | Tumour |
|---|---|---|---|
| t(9;22) | BCR-ABL1 | Constitutive tyrosine kinase | Chronic myeloid leukaemia (also some ALL) |
| t(8;14) | MYC-IGH | MYC overexpression | Burkitt lymphoma |
| t(14;18) | IGH-BCL2 | Blocks apoptosis | Follicular lymphoma |
| t(11;14) | CCND1-IGH | Cyclin D1 overexpression | Mantle cell lymphoma |
| t(15;17) | PML-RARA | Blocks myeloid maturation | Acute promyelocytic leukaemia |
| t(11;22) | EWSR1-FLI1 | Aberrant transcription factor | Ewing sarcoma |
| inv(2) | EML4-ALK | Constitutive kinase | Lung adenocarcinoma |
Clinical notes
- Endemic Burkitt lymphoma is linked to EBV and malaria in equatorial Africa; sporadic and immunodeficiency-related forms occur worldwide.
- Acute promyelocytic leukaemia is a haematological emergency because of disseminated intravascular coagulation; its translocation predicts an excellent response to retinoic acid.
In the lab
- Karyotype shows large translocations; FISH detects fusions and amplifications (HER2, N-MYC, BCR-ABL) on interphase nuclei.
- RT-PCR quantifies BCR-ABL transcripts to monitor response in chronic myeloid leukaemia.
- Next-generation sequencing panels detect fusions (ALK, ROS1, NTRK) that guide targeted therapy.
Test yourself
Think of the answer, then tap the question to see it.
Which translocation is typical of Burkitt lymphoma?
t(8;14), which places MYC under control of the immunoglobulin heavy chain locus.
What fusion gene drives Ewing sarcoma?
EWSR1-FLI1, from t(11;22).
How does promoter hypermethylation cause cancer?
It silences tumour suppressor genes (such as MLH1 or CDKN2A) without changing their DNA sequence.
Which technique detects HER2 amplification on tissue sections?
FISH (or immunohistochemistry for HER2 protein overexpression, with FISH for equivocal cases).
Related
- Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know
- Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis
- Molecular pathology: PCR, FISH, sequencing and liquid biopsy
- Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum
- Evading cell death and replicating without limit: BCL2 and telomerase
- Tumours of infancy and childhood
Related conditions
- Chronic myeloid leukaemia
- Non-Hodgkin lymphoma
- Ewing sarcoma
- Neuroblastoma
- Acute leukaemia (AML and ALL)
- Breast cancer
- Lung cancer
- Glioblastoma
- Lynch syndrome (hereditary non-polyposis colorectal cancer)
- Myelodysplastic syndromes
- Soft tissue sarcomas (liposarcoma, leiomyosarcoma, rhabdomyosarcoma)
Elsewhere in DurgiPedia
- Epigenetics: DNA and histone methylation
- FISH (fluorescence in situ hybridization)
- Polymerase chain reaction (PCR)
- 5-Methylcytosine
Microorganisms
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: ABL1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); What is epigenetics?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); The Genetics of Cancer (National Cancer Institute (NCI), 2026); Targeted Therapy to Treat Cancer (National Cancer Institute (NCI), 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.