Opinion Article - Journal of Cell Science and Mutations (2023) Volume 7, Issue 3
The role of mutational burden in tumour heterogeneity and evolution
Department of Evolution, Columbia University, New York, USA
- Corresponding Author:
- Yeul Nunes
Department of Evolution
Columbia University, New York, USA
Received: 24-Apr-2023, Manuscript No. AAACSM-23-97315; Editor assigned: 25-Apr-2023, PreQC No. AAACSM-23-97315(PQ); Reviewed: 09-May-2023, QC No.AAACSM-23-97315; Revised: 13-May-2023, Manuscript No. AAACSM-23-97315(R); Published: 20-May-2023, DOI:10.35841/AAACSM-7.3.148
Citation: Nunes Y. The role of mutational burden in tumour heterogeneity and evolution. J Cell Sci Mut. 2023;7(3):148
Tumors are complex and heterogeneous ecosystems composed of genetically diverse cell populations. The genetic diversity of tumors is due to the accumulation of mutations in tumor cells. The mutational burden, or the number of mutations present in the tumor genome, is a key determinant of tumor heterogeneity and evolution. This article explores the role of mutational burden in tumor heterogeneity and evolution. Mutational burden is a measure of the number of mutations present in a tumor genome. Tumors with high mutational burden are characterized by a high degree of genetic diversity, or heterogeneity. This heterogeneity arises from the accumulation of mutations in different cell populations within the tumor. Tumor heterogeneity has important clinical implications, as it can affect the response of tumors to therapy. For example, tumors with high mutational burden are more likely to respond to immunotherapy, which harnesses the immune system to target cancer cells .
Mutational burden also plays a critical role in tumor evolution. Mutations that confer a growth advantage to tumor cells can accumulate and drive tumor progression. This process, known as clonal evolution, leads to the emergence of dominant tumor cell populations that are resistant to therapy. Mutational burden can also affect the rate of tumor evolution. Tumors with high mutational burden are more likely to accumulate mutations that confer a growth advantage, leading to more rapid tumor evolution and progression. The role of mutational burden in tumor heterogeneity and evolution has important implications for cancer treatment. Strategies that target the genetic diversity of tumors, such as combination therapies that target multiple mutations, may be more effective than therapies that target a single mutation .
In addition, the use of biomarkers to identify tumors with high mutational burden may help to identify patients who are more likely to respond to immunotherapy. Advances in genomic sequencing technologies are enabling the identification of new biomarkers that can be used to guide cancer treatment. Mutational burden is a key determinant of tumor heterogeneity and evolution. Tumors with high mutational burden are more heterogeneous and more likely to evolve and progress. Understanding the role of mutational burden in tumor biology is essential for the development of new approaches to cancer diagnosis and treatment. Research has shown that tumors with high mutational burden are more responsive to immunotherapy, which targets the immune system to recognize and attack cancer cells. This is because high mutational burden creates a greater diversity of antigens, or markers on cancer cells that can be recognized by the immune system, making it more difficult for tumors to evade immune attack [3,4].
However, tumor heterogeneity also presents a challenge for cancer treatment, as different cell populations within a tumor may have different responses to therapy. For example, some cells may be resistant to chemotherapy or radiation, while others may be susceptible. This can lead to the emergence of drug-resistant subpopulations within the tumor, leading to treatment failure. Understanding the role of mutational burden in tumor evolution can also help to identify new therapeutic targets. For example, mutations that drive tumor progression may be targeted with drugs that inhibit specific signaling pathways. Alternatively, strategies that aim to induce tumor cell death by targeting vulnerabilities associated with high mutational burden may also be effective .
In conclusion, the role of mutational burden in tumor heterogeneity and evolution is a complex and dynamic process that has important implications for cancer diagnosis and treatment. Advances in genomic sequencing technologies and the identification of new biomarkers are enabling researchers to better understand the role of mutational burden in tumor biology, and to develop new approaches to cancer treatment that target the genetic diversity of tumors.
- Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nature reviews Clinical oncology. 2018;15(2):81-94.
- Lawson DA, Kessenbrock K, Davis RT, et al. Tumour heterogeneity and metastasis at single-cell resolution. Nat Cell Biol. 2018;20(12):1349-60.
- Haffner MC, Zwart W, Roudier MP, et al. Genomic and phenotypic heterogeneity in prostate cancer. Nat Rev Urol. 2021;18(2):79-92.
- Prasetyanti PR, Medema JP. Intra-tumor heterogeneity from a cancer stem cell perspective. Mol Cancer. 2017;16(1):1-9.
- McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: Past, present, and the future. Cell. 2017;168(4):613-28.