Hopkins research finds cancer “fingerprint”

Just like Miley Cyrus came in like a wrecking ball, cancer often comes in the same way, wanting only to break your walls. Although Miley never hit so hard in love, cancer has been hitting the human body hard since the beginning of time. But a year and a day after Miley closed her eyes and swung, a team of researchers published a study online in Genome Medicine that could leave cancer cells crashing in a blazing fall and lamenting “all you ever did was wreck me; yeah, you, you wreck me!”

Led by Andrew Feinberg, a professor at the Hopkins School of Medicine, and Rafael Irizarry, a professor at Harvard, the researchers found that cancers inflict widespread changes to the epigenome, regardless of their stage or type. The epigenome is the record of the chemical changes to an organism’s DNA and histones, the proteins that DNA wraps around. These epigenetic changes do not alter the DNA sequence itself; instead, they occur via adding or removing chemical groups, such as methyl groups or a histone modification. The changes can then be passed down to an organism’s offspring. 

The study found that an expansive variety of cancers wreaked extensive and distinctive havoc to methyl groups attached to the DNA. Methyl groups are chemical groups on DNA that serve as markers to help decide if a gene is switched “on” or “off,” ultimately determining how the cell behaves. Methyl groups and other such chemical markers on DNA are described as “epigenetic” and collectively make up the epigenome.

In 1983, Feinberg, along with Bert Vogelstein, another professor at the Hopkins School of Medicine, first pinpointed abnormal methylation in select cancers. Since then, Feinberg’s and other research groups have uncovered other cancer-associated changes in the epigenome. However, only recently were the researchers able to discover exactly how far-reaching these changes are.

In order to perform their study, Feinberg and Irizarry’s team gathered DNA samples from breast, colon, lung, pancreas and thyroid tumors, In addition to DNA samples from healthy tissue, the researchers the analyzed methylation patterns on the DNA. The analysis results indicated that all of the cancerous tumors had large sections of DNA with cancer-associated randomized methylation, leading to the loss of methylation over larger regions and the gain of methylation over smaller regions. Since these abnormalities arise early in cancer development, they may collaborate with genetic mutations to elicit cancer development.

The researchers found that the methylation patterns on the genomes of cancerous cells versus healthy cells were very different, regardless of the type of solid tumor. They believe that the alterations in the methylation patterns occurred very early in tumor formation, enabling tumor cells to adapt to environmental changes and thrive by quickly switching their genes on or off.

This means that cancerous cells have a toolbox that healthy neighboring cells lack, which gives the cancer cells a competitive advantage. The researchers concluded that since cancer can easily turn genes “on” or “off” as needed, they can turn on genes that are normally limited to early development and allow cancer cells to spread and invade healthy tissue, while turning off genes that cause dangerous cells to self-destruct.

The findings of this study provide important implications for early detection and prevention of cancer. The newfound insights into the cancer genome suggest that the distinctive methylation “fingerprint” could potentially be used to differentiate early-stage malignant cancers from benign growths. In the future, the researchers hope to find a way to prevent the transition from a benign to a cancerous fingerprint from occurring altogether.