title: Comparative genomic hybridization on microarray (a-CGH) in constitutional and acquired mosaicism may detect as low as 8% abnormal cells.
abstract: BACKGROUND
  The results of cytogenetic investigations on unbalanced chromosome anomalies, both constitutional and acquired, were largely improved by comparative genomic hybridization on microarray (a-CGH), but in mosaicism the ability of a-CGH to reliably detect imbalances is not yet well established. This problem of sensitivity is even more relevant in acquired mosaicism in neoplastic diseases, where cells carrying acquired imbalances coexist with normal cells, in particular when the proportion of abnormal cells may be low.We constructed a synthetic mosaicism by mixing the DNA of three patients carrying altogether seven chromosome imbalances with normal sex-matched DNA. Dilutions were prepared mimicking 5%, 6%, 7%, 8%, 10% and 15% levels of mosaicism. Oligomer-based a-CGH (244 K whole-genome system) was applied on the patients' DNA and customized slides designed around the regions of imbalance were used for the synthetic mosaics.
  
  
  CONCLUSIONS
  The a-CGH on the synthetic mosaics proved to be able to detect as low as 8% abnormal cells in the tissue examined. Although in our experiment some regions of imbalances escaped to be revealed at this level, and were detected only at 10-15% level, it should be remarked that these ones were the smallest analyzed, and that the imbalances recurrent as clonal anomalies in cancer and leukaemia are similar in size to those revealed at 8% level.
authors.affiliation: Biologia e Genetica, Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università dell'Insubria, Varese, Italy. emanuela.maserati@uninsubria.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Valli
authors.forename: Cristina
authors.initials: C
authors.lastname: Marletta
authors.forename: Barbara
authors.initials: B
authors.lastname: Pressato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalbano
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Curto
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasquali
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maserati