Heterogeneous Tumors
Written by Rhiana Devadasan
Tumor heterogeneity = describes the observation that different tumor cells can show distinct morphological and phenotypic profiles (including cellular morphology, gene expression, metabolism, motility, proliferation & metastatic potential).
This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity).
A minimal level of intra-tumour heterogeneity is a simple consequence of the imperfection of DNA replication: whenever a cell (normal or cancerous) divides, a few mutations are acquired—leading to a diverse population of cancer cells
Can be seen in:
- Leukaemias
- Breast, prostate, colon, brain, oesophagus, head and neck, bladder and gynaecological carcinomas
- Liposarcoma
- Multiple myeloma
Models of heterogeneity
- Cancer stem cells
- Within a cluster of tumour cell, only a small subset of cells are tumorigenic
- These cells are called: cancer stem cells (CSCs)
- They hold the ability to both self-renew and differentiate into non- tumorigenic progeny
- Clonal evolution
- In this model, tumours arise from a single mutated cell, accumulating additional mutations as it progresses.
- These changes give rise to additional subpopulations, and each of these subpopulations has the ability to divide and mutate further
- Linear expansion
- Sequentially ordered mutations
- Accumulate in driver genes, tumour suppressor genes, and DNA repair enzymes, resulting in clonal expansion of tumour cells
- Branched expansion
- Expansion into multiple subclonal populations occurs through a splitting mechanism
- This method is more associated with tumour heterogeneity than linear expansion
- The acquisition of mutations is random as a result of increased genomic instability with each successive generation
- The long-term mutational accumulation may provide a selective advantage during certain stages of tumour progression
Causes of heterogeneity
- Genetic
- Exogenous
- Mutagenic factors such as: UV radiation (skin cancers) and tobacco (lung cancer).
- Endogenous
- Key regulatory pathways are disrupted in the cells
- Impaired DNA repair mechanisms
- Defects in mitosis cycle