The use of whole genome amplification to study chromosomal changes in XXXX : insights into genome-wide signature of preneoplasia associated with @entity5 progression.

@entity263 @entity5 @entity189 @entity854 @entity420 @entity1865 @entity5436
BACKGROUND: @entity263 (CaP) is a disease with multifactorial etiology that includes both genetic and environmental components. The knowledge of the genetic basis of CaP has increased over the past years, mainly in the pathways that underlie tumourigenesis, progression and drug resistance. The vast majority of cases of CaP are @entity420 that likely develop through a pre-malignant lesion and @entity5436 ( @entity5436 ). Histologically, CaP is a heterogeneous disease consisting of multiple, discrete foci of @entity189 and @entity5436 that are commonly interspersed with benign glands and stroma. This admixture with benign tissue can complicate genomic analyses in CaP. Specifically, when DNA is bulk-extracted the genetic information obtained represents an average for all of the cells within the sample. RESULTS: To minimize this problem, we obtained DNA from individual foci of @entity5436 and CaP by laser capture microdissection (LCM). The small quantities of DNA thus obtained were then amplified by means of multiple-displacement amplification ( @entity1865 ), for use in genomic DNA array comparative genomic hybridisation (gaCGH). Recurrent chromosome @entity854 ( @entity854 ) were observed in both @entity5436 and CaP. In @entity5436 , chromosomal imbalances involving chromosome 8 where common, whilst in CaP additional chromosomal changes involving chromosomes 6, 10, 13 and 16 where also frequently observed. CONCLUSION: An overall increase in chromosomal changes was seen in CaP compared to @entity5436 , suggesting a universal breakdown in chromosomal stability. The accumulation of @entity854 , which occurs during this process is non-random and may indicate chromosomal regions important in tumourigenesis. It is therefore likely that the alterations in copy number are part of a programmed cycle of events that promote @entity5 development, progression and survival. The combination of LCM, @entity1865 and gaCGH is ideally suited for the identification of @entity854 from small cell clusters and may assist in the discovery of potential genomic markers for early diagnosis, or identify the location of @entity5 suppressor genes (TSG) or oncogenes previously unreported in @entity5436 and CaP.
