Cancer-causing mutations in the human genome have been a subject of intense research over the past decade. With increasing numbers of mutations identified and linked to individual cancers, the possibility of treating individual patients with a customized treatment plan based on their individual cancer genome is quickly becoming a reality.

Cancer arises when individual cells acquire mutations in their DNA. These mutations allow cancerous cells to proliferate uncontrollably, aggressively invade surrounding tissues, and metastasize to distant locations. Based on this progression, a potentially tremendous implication emerges: if every type of cancer arises from an ancestor cell that acquires a single mutation, then scientists should be able to trace every type of cancer back to its original mutation through modern genomic sequencing technologies. High volumes of the human genome have been analyzed in search of these ancestor mutations using a variety of techniques, the most common of which is a large Polymerase Chain Reaction (PCR) screen. In this type of study, DNA of up to one hundred cancer patients is sequenced; the sequences are then analyzed for repeating codons, the DNA units that determine single amino acids in a protein. Analyzing the enormous volume of data from these screens requires the efforts of several institutions. The first 90 cancer-causing mutations were identified at the Johns Hopkins Medical Institute, where scientists screened 11 breast cancer and 11 colorectal cancer patients’ genomes.3 After this study was published in 2006, researchers found these 90 mutations across every known type of cancer. These findings stimulated even more ambitious projects: if the original cancer-causing mutations are identified, scientists may be able to reverse the cancer process by removing faulty DNA sequences using precisely targeted DNA truncation proteins.

However, such a feat is obviously more easily said than done. One of the many obstacles in identifying cancer genomes is the fact that approximately 10 to 15% of cancers derive large portions of their DNA from viruses such as HIV and Hepatitis B. The addition of foreign DNA complicates the search for the original mutation, since viral DNA and RNA are propagated in human cells. This phenomenon masks human mutations that may have existed before the virus entered the host cell. In addition, because tumors are inherently unstable, cancers may lose up to 25% of their genetic code due to errors in cell division, making the task of tracing them even more difficult. Finally, the mutations in every individual cancer have accumulated over the patient’s lifetime; differentiating between mutations of the original cancerous cell line and those caused by aging and environmental factors is an arduous task.

In order to overcome these challenges, scientists use several approaches. First, they increase the sample size—this strategy ensures that the mutations are not specific to an individual organism or geographic area but are common in all patients with that type of cancer. Second, accumulated data concerning viral genomes allow scientists to screen for and mark the areas of viral origin in patients’ DNA. Several advances have already been made despite the difficulties: for instance, in endometrial cancer—a cancer originating in the uterine lining—mutations in the Nucleotide Excision Repair (NER) and MisMatch Repair (MMR) genes have been found to occur in 13% of all affected patients.4 NER and MMR are involved in DNA repair mechanisms and act as the body’s “guardians” of the DNA replication process. In a healthy individual, both NER and MMR ensure that each new cell receives a complete set of functional chromosomes following cell division. In a cancerous cell, these two genes acquire a mutation that permits replication of damaged and mismatched DNA sequences. Similarly, mutations in the normally tumor-suppressing Breast Cancer Type 1 Susceptibility Gene 1 and Gene 2 (BRCA1 and BRCA2) have been identified as major culprits in breast cancer. In prostate cancer, E-26 Transformation Specific (ETS) and Transmembrane Protease, Serine 2 (TMPRSS2) are two DNA transcription regulatory proteins discovered to initiate the disease process.5

One of the latest frontiers in cancer treatment is the identification and study of individual, disease-causing mutations. Thousands of tumor genomes have been sequenced to discover recurring mutations in each cancer, and tremendous advances have been made in this emergent field of cancer genomics. Further study will ultimately aim to tailor cancer treatment to the patient’s specific set of mutations in the emerging field of personalized medicine. This strategy is already being used in the treatment of leukemia at the Cincinnati Children’s Hospital, where a clinical study has been underway since August 2013.2 This trial uses a combined treatment program that includes standard drug therapy while targeting a specific mutation in the mTOR gene, which is responsible for DNA damage repair. Thus, less than a decade after researchers first began to identify unique cancer-causing mutations, treatment programs tailored to patient genomes are becoming a reality.


  1. Lengauer, C. et al. Nature 1998, 396, 643-649.
  2. Miller, N. (accessed Nov 9, 2013).
  3. Sjöblom, T. et al. Science 2006, 314, 268-274.
  4. Stratton, M. et al. Nature 2009, 458, 719-724.
  5. Tomlins, S. et al. Science 2005, 310, 644-648.