Researchers from the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center have completed the first genetic sequence of a brain cancer cell line. The line, U87, is a popular research model that is in use at UCLA and various other research institutions. According to UCLA, the sequence brings researchers one step closer toward personalized treatments based on specific molecular targets affecting this line.
"This is very exciting because we, as scientists, can now move forward with revealing complete cancer genomes," lead researcher Stan Nelson, professor of human genetics at UCLA, said in a press release. "Cancer is at its heart a genetic disease. Cancer cells have acquired mutations that allow them to invade tissues and to not live by the normal rules. The changes from normal [sequences] that have given the cancer these special properties are encoded in DNA, and the entire DNA sequence has just been too complex and costly to decode until now."
Nelson’s team completed the sequence using Applied Biosystems’ SOLiD sequencing system, which uses a ligation-based assay with two-base color-encoded oligonucleotides that enabled detection of single nucleotide variants, insertions, and deletions. The researchers’ efforts generated 30x coverage of the genomic sequence using a 50-base paired-end strategy. According to UCLA, the cell line was sequenced in less than a month for a reported total cost of $35,000.
According to Nelson, the sequence revealed most, if not all, chromosomal translocations and genetic mutations that lead to this cancer’s development. "This was the most thorough sequencing analysis of an individual cancer cell line that has been performed to date," said Nelson.
According to Nelson, the researchers chose the U87 cell line because since it has already been thoroughly analyzed, it allows researchers to go back and evaluate past findings to determine how to move forward. “As scientists, we previously didn't know most of the mutations that occur within a given cancer—we're blind to them,” he said. “Now, this new [sequencing] technology allows us to look at every single cancer and decode the cancer genome completely so there's no chance we're missing a mutation that may be causing the disease."
The study could help researchers develop a better way to monitor the recurrence of brain cancers, which would enable earlier diagnosis and treatment. Knowledge of the genes that are mutated and driving the cancer’s growth could also help oncologists select therapies best suited to attack the molecular signature of their patient’s specific disease.
The researchers will continue investigating the genetic sequences of cancer cell lines. Nelson said that in the long-term, he would like to develop the ability to sequence a patient’s individual cancer, and turn the data around quickly enough to give oncologists the ability to make treatment decisions based on the cancer’s specific sequence.
"Oncologists would be able to know, definitively, when they can stop giving chemotherapy because it's no longer needed or when they have to resume chemotherapy because the cancer has returned," said Nelson.
Funding was provided by the National Institutes of Health. The paper, “U87MG decoded: the genomic sequence of a cytogenetically aberrant human cancer cell line,” was published Jan. 29 online at PLoS Genetics.
