Roche microarrays further ALL knowledge

In acute lymphoblastic leukemia, the most common subsequent mutation is a partial deletion of chromosome 12p, or del(12p). To further define the  timing and structure of the del(12p) "secondary hit" associated with  ALL, researchers analyzed samples from participants in an epidemiologic  research study focused on the etiology of childhood leukemia in a  35-county area in California, USA. Roche NimbleGen, a division of the  Swiss drug major, provided a custom human CGH 385K microarray consisting  of 50bp long oligonucletide probes tiled across the 38Mb p-arm of  chromosome 12, which enabled the characterization of chromosome deletion  breakpoints at sub-kilobase resolution.

Of the 10 samples analyzed using NimbleGen CGH arrays, all showed the  TEL-AML1 translocation and nine had a deletion of the second TEL allele  by fluorescent in situ hybridization (FISH) analysis. The higher  resolution NimbleGen CGH array revealed interstitial deletions within  the chromosome 12 p-arm in four samples, and single breakpoints with  deletion of the remainder of the chromosome arm in five samples. In  addition, array CGH revealed an unexpected association of del(12p)  rearrangements with SINE and LINE retrotransposons in the human genome.  The results of Weimels' study provides additional support for the for  "two-hit hypothesis," stating that the TEL-AML1 translocation is a  pre-natal occurrence and del(12p) is a post-natal, secondary event in  more mature cells with a structure that suggests the involvement of  retrotransposon instability.

Gerd Maass, chief executive of Roche NimbleGen, said: "the use of  NimbleGen arrays in hematological studies like these clearly  demonstrates the enormous potential of microarrays to rapidly screen and  discern significant differences among populations and individuals at the  molecular level. Each chromosomal gain or loss, genetic abnormality or  other mutagenic event contributes to the full context of a disease  pathway, regardless of whether it's the first, second or 20th cumulative  hit. Roche NimbleGen is committed to providing researchers with these  essential laboratory tools to help discover the origins and causes of  such diseases."