Several new studies have explored the link between jumping genes (transposons) and the ability to cause cancer in the body, once the jumping gene is inserted into specific segment of the genetic code. THe studies originating from John Hopkins University have focused on insertions of a stretch of DNA called the LINE-1 transposon, which can produce copies of itself into new areas of the genome and may interrupt normal DNA sequences.
The human genome consists of a number of DNA combinations and an estimated 17% is made up of LINE-1 copies. Previous published cases have defined cases in which new LINE-1 insertions disabled cancer-fighting genes inside tumors.
“A challenge we had to overcome to begin to answer that question was detecting new copies of LINE-1 when the human genome already contains so many — it was like finding a needle in a haystack,” said Haig Kazazian, M.D. , professor of molecular biology and genetics at the Johns Hopkins University School of Medicine’s McKusick-Nathans Institute for Genetic Medicine.
The scientists used a genetic sequencing technique to find LINE-1 insertions and analyzed the insertions in several types and stages of gastrointestinal biopsies. DNA insertions found in colon, pancreatic and gastric cancer were compared to those in healthy tissue from the same people. The study findings, published in the journal Genome Research, revealed that new insertions of the still-mobile LINE-1 transposons tended to occur early in cancer development. In total 29 new insertions were found in colon polyps, and 24 new insertions were found in samples from seven patients with pancreatic cancer. Of those, 13 were found in both the primary cancer and metastasized cancer cells, indicating that they had occurred before the tumor metastasized.
The second study, published in Nature Medicine, has revealed LINE-1 insertions in pancreatic cancer. Tissues obtained from autopsy results of 22 people diagnosed with pancreatic cancer revealed that 21 of the cancers had LINE-1 insertions not found in the control group consisting of health patients. LINE-1 insertions tended to occur more in metastasized tumors than in primary tumours.
The third study examined LINE-1 insertions in esophageal cancer and a condition known as Barrett’s esophagus, a precursor to cancer. New insertions were found in some but not all patients whose Barrett’s esophagus had not progressed to cancer after 15 or more years, and patients with both Barrett’s esophagus and cancer.
“The key question is whether these insertions are driving cancer development or whether they are just a byproduct of cancer,” said Kazazian.