Cancer genome sequencing analyzes the entire genetic information, or genome, within a patient’s cancer cells. This process provides a comprehensive understanding of the unique genetic alterations present in a tumor, which differ significantly from person to person. By examining DNA and RNA sequences, scientists identify specific changes that drive cancer growth and behavior, creating a detailed genetic blueprint of each patient’s tumor.
Genetic Foundations of Cancer
DNA, or deoxyribonucleic acid, serves as the instruction manual for every cell in our bodies, dictating its functions, growth, and division. These instructions are organized into segments called genes, which contain the code for building proteins. Proteins perform a vast array of tasks within the cell, including regulating cell growth and division.
Normally, cells grow and divide in a controlled manner, allowing the body to grow and repair itself. However, mistakes, known as mutations, occur when DNA is copied during cell division. These mutations are changes in the DNA sequence that can alter how proteins function.
While some mutations are inherited, most occur after birth due to environmental factors like tobacco smoke or UV radiation, or from random errors during cell division. These acquired mutations accumulate over time, increasing cancer risk.
Certain gene types are particularly relevant to cancer development. Proto-oncogenes promote cell growth but can become oncogenes when mutated, leading to uncontrolled division. Tumor suppressor genes restrict cell growth; their inactivation by mutation can result in unchecked cell proliferation. DNA repair genes correct DNA errors; if mutated, other errors may go uncorrected, allowing cells to become cancerous. Cancer is fundamentally a disease driven by these acquired genetic changes that disrupt normal cell regulation.
The Process of Cancer Genome Sequencing
Cancer genome sequencing begins by obtaining a sample from the patient, often a tumor biopsy, or sometimes blood or other bodily fluids. DNA and sometimes RNA are extracted from this sample. The quality and quantity of the extracted genetic material influence sequencing success.
Once the DNA is extracted, specialized machines called next-generation sequencers “read” the genetic code. This technology allows for the simultaneous analysis of millions of DNA fragments. The raw sequencing data is then processed and aligned to a reference human genome to identify differences, which represent the genetic alterations within the cancer cells.
Several sequencing approaches are used in cancer genomics.
Whole Genome Sequencing (WGS)
WGS analyzes nearly all of a cell’s DNA, providing a comprehensive view of genetic changes, including those in non-coding regions.
Whole Exome Sequencing (WES)
WES focuses specifically on the exome, which contains the protein-coding regions of genes. The exome accounts for about 2% of the genome but contains most known disease-causing mutations.
Targeted Sequencing
Targeted sequencing, also known as panel sequencing, examines a pre-selected set of genes or specific regions known to be associated with cancer. This approach is more focused and cost-effective, offering higher sequencing depth for those particular areas.
These methods aim to uncover various genomic alterations:
- Single nucleotide variants (small changes in a single DNA building block)
- Insertions or deletions of DNA segments
- Copy number variations (changes in the number of copies of a gene)
- Gene fusions (when two genes abnormally join together)
Translating Insights into Treatment
Genomic information from cancer genome sequencing guides treatment decisions in the clinical setting. This data enables a personalized medicine approach, tailoring therapies to a patient’s unique tumor genetic profile. Identifying specific mutations helps predict how a tumor might respond to or resist certain treatments.
For example, in non-small cell lung cancer, detecting epidermal growth factor receptor (EGFR) mutations can guide the use of EGFR inhibitors, which are targeted therapies designed to block the activity of specific proteins involved in cancer growth. Similarly, identifying BRAF mutations in melanoma or HER2 amplification in breast cancer allows for the selection of specific therapies that target these alterations. This precision in treatment selection can lead to improved objective response rates and longer progression-free survival compared to standard treatments.
Beyond guiding targeted therapies, genomic insights can refine a cancer diagnosis, provide information about a patient’s likely prognosis, and help monitor disease progression or detect resistance mechanisms. Cancer genome sequencing is also valuable in clinical trials, helping identify eligible patients who may benefit from investigational therapies based on their tumor’s specific genetic alterations. This integration of genomics into patient care transforms cancer treatment, moving towards more effective and individualized therapeutic strategies.