By Justin Petrone

After years of selectively offering array-based tests to patients, some European clinical cytogenetic labs have recently begun using arrays as the primary sample-analysis tool in their services, rather than traditional cytogenetic methods like molecular karyotyping or fluorescent in situ hybridization.

According to several European cytogeneticists interviewed by BioArray News, the switch to arrays occurred over the past year as a result of falling array prices and because lab techs have become more confident in their ability to interpret results as they have gained more experience with the technology.

"In the beginning, only patients with a normal cytogenetic karyotype were allowed to continue on with array analysis," said Nicole deLeeuw, a clinical cytogeneticist at the Radboud University Nijmegen Medical Center Department of Human Genetics in the Netherlands.

"Now, in at least three centers in the Netherlands, we decided to put arrays first because basically you get a three-in-one outcome within one test," she said. "Instead of cytogenetics and FISH and [multiplex ligation-dependent probe amplification screening], with genome-wide array analysis, you can pick up all imbalances with one test."

DeLeeuw said the other Dutch centers that have decided to put arrays first are the Department of Human Genetics at the University Medical Center Groningen and the Center for Human and Clinical Genetics at Leiden University Medical Center.

Trijnie Dijkhuizen, a clinical cytogenetist at Groningen, confirmed with BioArray News that her lab decided last year to screen patient samples with arrays before using other technologies, saying arrays "are first, and in addition we do some cytogenetics," referring to FISH and MLPA.

According to Dijkhuizen, "all eight" academic medical centers in the Netherlands that provide clinical cytogenetic services offer array diagnostics, though they are in different stages of adopting the technology. In addition to Nijmegen, Groningen, and Leiden, the other five centers that offer array-based testing are the Department of Clinical Genetics at University Hospital Maastricht; the Institute of Clinical Genetics at Erasmus MC in Rotterdam; the University Medical Center Utrecht; the VU University Medical Center in Amsterdam; and the Academic Medical Center at the University of Amsterdam.

Across the border in Belgium similar protocol shifts are underway. Joris Vermeesch, associate professor at the Department of Human Genetics at the University of Leuven, told BioArray News this week that clinical cytogeneticists who send samples to Leuven for analysis are now requesting arrays first, while Björn Menten of the Center for Medical Genetics at Ghent University Hospital said his facility is increasingly using arrays in a clinical setting.

Like Nijmegen's deLeeuw, Menten and colleagues first started using arrays as the primary technology about six years ago for research purposes, and have recently begun using the tools in the clinic.

"In the beginning, we selected patients for array analysis. Now that prices are dropping, we can offer it to everyone," Menten told BioArray News. "Really, since the beginning of 2009, it has completely moved to diagnostics. [For instance,] in postnatal cases it is replacing normal karyotyping. All patients will now have microarray analyses performed."

Early Adopters

According to Vermeesch, cytogenetic labs in the Netherlands and Belgium have been among the earliest adopters of array technology in Europe, though there are other "leading laboratories" that have begun using the technology, including the Department of Molecular Medicine at the Karolinska Hospital in Stockholm, Sweden; and the Cyprus Institute of Neurology and Genetics in Nicosia.

In Vermeesch’s lab, the switch to arrays has evolved over more than six years. In the past, Vermeesch has used both bacterial artificial chromosome arrays as well as oligonucleotide-based chips to analyze neonatal samples, but in June he began evaluating arrays designed by Oxford Gene Technology for prenatal diagnostics (see BAN 6/30/2009).

At Nijmegen, arrays took a similar route into the clinic. "We started offering these services in 2003 and we had a solid report at the end of 2004," deLeeuw said. "In 2003 and 2004, the numbers of requests were limited and only clinical geneticists were able to ask for array-based diagnostics in a very selective population of patients. We did that partly because we wanted to gain experience and offer them more than routine cytogenetic analysis."