Combining array‐based approaches for the identification of candidate tumor suppressor loci in mature lymphoid neoplasms

Abstract

Nieländer I, Bug S, Richter J, Giefing M, Martín-Subero JI, Siebert R. Combining array-based approaches for the identification of candidate tumor suppressor loci in mature lymphoid neoplasms. APMIS 2007;115:1107-1134.Tumor suppressor gene (TSG) inactivation by chromosomal deletions and/or mutations is a wellcharacterized genetic alteration in lymphomas. Array-based technologies have greatly increased the detection and characterization of chromosomal imbalances and regions with loss of heterozygosity (LOH), leading to the identification of a number of novel candidate TSG loci. In addition, microarray platforms for studying DNA methylation and histone modifications enable identifying epigenetic changes affecting gene expression of TSG. Combining these microarray technologies with gene expression profiling is a promising strategy to discover novel TSG in regions targeted by genetic or epigenetic alterations. In this review we present an outline of methodological aspects of the various microarray technologies, and discuss their potentials and restrictions. Furthermore, we survey research findings derived from these high-throughput techniques, which are allowing a deeper insight into the mechanisms of lymphomagenesis.

Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma by array-based comparative genomic hybridization

“…bacterial artificial chromosome [BAC] arrays, cDNA arrays, oligonucleotide arrays) have been developed. [15][16][17][18] Array CGH analyses of cHL have so far been focused on a few well-characterized cHL cell lines, 19 which were all established from relapsed cases after treatment.…”

Genome-Wide DNA Methylation Profiles in Renal Tumors of Various Histological Subtypes and Non-Tumorous Renal Tissues

“…Many researchers in the field of cancer epigenetics have used promoter arrays to identify the genes that are methylated in cancer cells [23][24][25] . However, the promoter regions of specific genes are not the only target of DNA methylation alterations in human cancers.…”

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

“…In the initial CGH arrays, the metaphase spreads were substituted by DNA fragments cloned in plasmid, bacterial, or yeast artificial chromosomes, and more recently by long oligonucleotides (50-75-mer). 1 The current high density oligonucleotide arrays cover the whole genome (WG) with probes spaced about 1-5 kb apart. The single-nucleotide polymorphism arrays (SNP arrays) are alternative platforms to the CGH arrays.…”

“…Both CGH and SNP arrays allow the detection of CNA at high resolution but both require approximately at least 30% of cells carrying the same abnormal region to be detected. 1 This sensitivity may turn into an advantage since it may filter out small irrelevant clones, although, on the other hand, it may miss small clones that may be important later on in the evolution of the disease. These platforms also allow the use of DNA extracted from routinely processed formalin-fixed and paraffin-embedded (FFPE) tissues.…”

“…One of the major applications of this genomic knowledge in the study of lymphoid neoplasms has been the design of different types of microarray platforms for the global analysis of DNA alterations and gene expression profiling (GEP). 1,2 The recent development of a new generation of sequencing technologies (next generation sequencing (NGS) or massively parallel sequencing) and their systematic application to human cancer and in particular to lymphoid neoplasms are revealing a landscape of somatic mutations of unprecedented complexity. 3 These studies already have provided a number of important findings with functional and clinical implications including new potential targets for advanced therapies.…”