Custom microarray developer NimbleGen will help a team of researchers at Cold Spring Harbor Laboratory commercialize a technology that profiles chromosomal insertions, deletions, and amplifications.
A team led by Rob Lucito and Michael Wigler used represent-ational oligonucleotide microarray analysis, or ROMA, to compare the DNA of normal cells and breast cancer cells and found a “striking” collection of chromosomal amplifications and deletions that are “likely” involved in some aspect of breast cancer. Though some of the amplifications and deletions correspond to known oncogenes and tumor-suppressor genes, “many of them are likely to reveal new genes and cellular functions involved in breast cancer or cancer in general,” the researchers explained.
To date, “most of the work” has been performed using printed arrays, though “we’ve started working with … NimbleGen Systems … that will make the arrays for us, and we’re investigating commercialization of that format,” Lucito told SNPtech Reporter, a sister publication of BioArray News.
In its research, the team said it was surprised when it performed normal-to-normal research instead of normal-to-tumor research and frequently detected chromosomal deletions and duplications 100 kb to 1 Mb in length in normal DNA samples. The researchers suggested that these variations among individuals, called “copy number polymorphisms,” might underlie many human traits, including disease predisposition or resistance.
The team’s research appears in the October issue of Genome Research.
To be sure, ROMA is more than 20 years old. In 1981, Wigler, working at Cold Spring Harbor, pioneered a gene-transfer method and discovered one of the first human oncogenes — H-ras. It has since been proven that excess Ras or alterations in cell functions related to the protein play a role in a majority of cancers. To that end, drug makers have begun testing cancer therapeutics designed to target components of the Ras pathway.
Ten years ago, Wigler and Cold Spring Harbor colleague Nikolai Lisitsyn developed a method to discover genes called representational difference analysis, which enabled researchers to clone the differences between any two sets of DNA — normal DNA versus tumor DNA isolated from the same patient, or uninfected cells versus cells infected with an unknown virus.
Since then, Wigler’s lab has used RDA to identify several previously unrecognized oncogenes and tumor-suppressor genes, primarily from sporadic breast cancers, according to Cold Spring Harbor. ROMA has therefore been called RDA on a chip: By combining RDA and microarray analysis, researchers can theoretically detect copy-number polymorphisms on a genome-wide scale.
Lucito said a timeline for commercialization has not yet been formulated. However, Emile Nuwaysir, director of business development at NimbleGen, said he hopes to make the technology broadly available to researchers within one year.
NimbleGen provides a gene-expression service to academia and drug developers, and has also recently begun providing a similar service for Lucito’s lab at Cold Spring Harbor. Nuwaysir said it is too early to say how NimbleGen will participate in the commercialization of the technology.