Cytogenetic Analysis of Non Hodgkin's Lymphomas by Ratio-Painting and Comparative Genomic Hybridization Reveals Unsuspected Chromosomal Abnormalities

Abstract

Cytogenetic analysis of cancer cells has proven to be a powerful tool in understanding malignant evolution and in providing clinically useful markers. In recent years the advent of new fluorescence in-situ hybridization (FISH) methods such as ratio-painting and comparative genomic hybridization (CGH) have enabled much more accurate karyotypes of malignant cells to be detected. In this study, we have examined the chromosomes present in malignant cells from a series of 6 low grade follicular centre and 2 high grade diffuse large cell non-Hodgkin^h lymphomas (NHL.) using conventional G-banding. In all cases chromosome abnormalities were observed, including the presence of marker chromosomes in six cases. The NHL cells were then subjected to the FISH method of ratio-painting. This provided a more accurate understanding of the origins of derivative chromosomes and identified the origins of all of the marker chromosomes. It also revealed hitherto unsuspected abnormalities. For example, in one case four abnormal chromosomes were demonstrated to contain material from chromosome 8, which had not been previously suspected from G-banding. Regions of amplification and deletion on the chromosomes were also investigated by CGH, which identitied further unsuspected chromosomal abnormalities. For example, in case L124, trisomy of chromosome 7 was confirmed by CGH, but an unsuspected amplification of 3(p12) was also revealed. These approaches demonstrate the power of FISH technology in providing a more precise analysis of malignant cell chromosomes, and in doing so have produced comprehensive karyotypes of the NHL. under study.

Key Words:

• Non-Hodgkin's lymphomas
• chromosomes
• fluorescence in-situ hybridization
• ratio-painting
• comparative genomic hybridization