Paper in PLoS Genetics suggests that well-studied cancer line is far more complex than previously thought.
A group of researchers have carried out what they claim is the first complete genomic sequencing of a glioblastoma cell line. They suggest their findings could dramatically improve the search for new drug targets and lead to the development of gene signature-specific treatments for brain cancer and the design of gene-based tests to monitor the success of anticancer treatments and cancer recurrence.
The UCLA Jonsson Comprehensive Cancer Center’s used the Applied Biosytems’ SOLiD System to sequence the U87MG glioblastoma cell line. The project took less than a month and cost about $35,000. The results are published in PLoS Genetics in a paper titled “U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line.”
The U87MG cell line is derived from a human grade IV glioma for which a wide range of biological information is already known, says lead author, Stanley Nelson, M.D. They point out that a characteristic of the U87MG cell line that differentiates it from samples used in other whole genome sequencing projects is its highly aberrant genomic structure.
The findings from the team’s sequencing efforts now suggest that U87MG is in fact “much more complex than previously thought based on lower resolution techniques.” Mutational analysis found that 512 genes were homozygously mutated, including 154 by single nucleotide variations (SNVs), 178 by small insertions/deletions (indels), 145 by large microdeletions, and up to 35 by interchromosomal translocations.
“Due to its heavily rearranged state, we thoroughly and accurately assessed each of these major classes of mutations and demonstrated that small indels, large microdeletions, and interchromosomal translocations are actually the major categories of mutations that affect known genes in this cancer cell line,” the researchers report.
Of the 2,384,470 SNVs and 191,743 small indels found in U87MG, a total of 332 genes were predicted to have loss-of-function, homozygous mutations as a consequence of small variants. Of these, 225 genes contained variants matching alleles annotated in version 129 of dbSNP (the NCBI’s database of SNPS), while 107 contained novel variants (eight SNVs and 99 indels) not observed in dbSNP.
The Jonsson Cancer Center researchers are setting up a website so scientists can access and retrieve the sequencing data.