Double minutes are small fragments of DNA that exist outside of the normal chromosomes within a cancer cell’s nucleus. These structures are a form of extrachromosomal DNA (ecDNA). Unlike the organized, linear structure of standard chromosomes, double minutes are copies of specific genetic instructions that have broken away from the main set. First observed over 50 years ago, their presence is a feature unique to cancer cells, distinguishing them from healthy cells.
What Are Double Minutes?
Double minutes are small, circular pieces of DNA that can be up to a few million base pairs in size. A defining characteristic is their lack of centromeres, the central hubs on normal chromosomes that anchor them during cell division. This structural difference is a primary reason for their unusual behavior.
Their name comes from their appearance under a microscope during a specific phase of cell division, where they look like small, paired dots. This paired appearance led to the “double” in their name, while “minutes” refers to their minuscule size compared to standard chromosomes. These fragments replicate within the cell’s nucleus, and the genes they carry can be expressed constantly due to a lack of normal regulation.
Formation and Function in Cancer Cells
The creation of double minutes results from gene amplification, where a chromosome segment is copied repeatedly. These repeated DNA segments can break off from the chromosome and form circular, self-replicating structures. This process can be triggered by events like major DNA damage or errors during DNA replication.
The primary function of double minutes is to house and promote the overexpression of oncogenes—genes that can cause cancer. An oncogene on a double minute continuously sends signals for the cell to divide, like a stuck accelerator pedal. A single cell can contain many copies, resulting in a high number of oncogenes and giving the cancer cell a proliferation advantage. Genes like MYC, a well-known oncogene, are frequently found on double minutes.
The random distribution of double minutes during cell division is another aspect of their function. When a cancer cell divides, these structures are not split evenly between the two new daughter cells. One might inherit many double minutes, while the other receives few or none. This allows a cancer cell population to become diverse quickly, helping the tumor evolve and adapt.
Clinical Significance in Cancer Diagnosis
In a clinical setting, the detection of double minutes in a patient’s tumor cells serves as an important biomarker. Their presence is strongly linked to aggressive, rapidly growing cancers and is generally considered an indicator of a poor prognosis.
The appearance of double minutes is not uniform across all malignancies; they are found more frequently in certain types of cancer. They are most notably observed in aggressive brain tumors like glioblastoma, a childhood cancer called neuroblastoma, and specific forms of lung, ovarian, and colon cancer. In blood cancers, double minutes are rarer but are still associated with a more severe form of the disease when present.
Challenges and Approaches in Treatment
The presence of double minutes presents a challenge for cancer therapy because they are a driver of drug resistance. Cancer cells can use them to quickly generate numerous copies of genes that counteract chemotherapy or targeted drugs. For example, if a drug targets a specific protein, the cell can amplify the gene for that protein, producing it in such large quantities that the drug becomes ineffective.
Because it is difficult to directly eliminate double minutes, current therapeutic strategies focus on the oncogenes they carry. Therapies such as kinase inhibitors are designed to interfere with the overexpressed proteins, shutting down the growth signals they produce. This approach targets the consequence of gene amplification rather than the underlying genetic structure.
Future cancer research is focused on finding ways to eliminate these extrachromosomal structures from tumor cells. Scientists are exploring mechanisms to induce the loss of double minutes, as studies show this can reduce a tumor’s ability to grow. Developing treatments that can specifically destroy cells containing double minutes could provide a new avenue for treating aggressive cancers.