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 representational 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.
In its research, the team said it was surprised when it performed normal-to-normal sample comparisons research instead of normal-to-tumor comparisons 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 has been in development for more than 20 years. In 1981, Wigler 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 find several previously unrecognized oncogenes and tumor-suppressor genes, primarily from sporadic breast cancers.
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. “We are very interested in helping [the lab] make [its] tools more broadly available,” Nuwaysir said. He said it is to early to say how NimbleGen will participate in the commercialization of the technology.