Screening of human placentas for chromosomal mosaicism using comparative genomic hybridization

Detection of confined placental mosaicism (CPM) in term placental tissues is usually accomplished by conventional cytogenetic analysis of cultured chorionic stroma and direct preparations from trophoblast or, more recently, by fluorescence in situ hybridization (FISH) on interphase nuclei. In this study, we describe the use of comparative genomic hybridization (CGH) for detection of chromosomal aneuploidy in term placentas and evaluate the sensitivity of this novel approach for CPM diagnosis in multiple placental samples acquired from five pregnancies prenatally diagnosed with CPM7 and CPM16. Each sample of placental villi was separated enzymatically into trophoblast and chorionic stroma, and the level of aneuploidy (three signals/nuclei) in each tissue was determined by FISH analysis, using centromeric DNA probes specific for chromosome 7 (D7Z1/Z2) or 16 (D16Z2). Aneuploidy levels ranged from 5.2-96.1% in the 11 tissues with CPM7 and 9.8-93% in the 29 tissues with CPM16. Subsequently, CGH analysis of DNA from the trophoblast and chorionic stroma of the same tissue sites detected the trisomic clone in all placental tissues with aneuploidy (16%, as determined by FISH analysis). Our results demonstrate the sensitivity of CGH analysis for detection of chromosomal aneuploidy mosaicism and support our contention that the CGH technique is the most effective cytogenetic method for screening term placentas for the presence of CPM.