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

Abstract

The development of high throughput technologies based on the knowledge of the human genome has opened the possibility to search for global genomic alterations in tumors responsible for their development and progression that may have important clinical implications. One of the major applications of this genomic knowledge has been the design of different types of microarray platforms for the analysis of DNA alterations and gene expression profiling (GEP). The main contributions of the DNA studies in lymphoid neoplasms include the definition of relatively characteristic genomic profiles for specific disease entities, the demonstration of common chromosomal alterations across entities, the identification of genes and pathways targeted by the altered chromosomal regions, and the identification of chromosomal alterations with prognostic implications. RNA GEP studies in these tumors have enhanced the molecular characterization of known entities and facilitated the recognition of new subtypes and categories of lymphoid neoplasms, the identification of new biomarkers and prognostic models, and the detection of oncogenic pathways with potential implications for targeted therapies. The recent development of the next generation sequencing (NGS) technologies and its application in lymphoid neoplasms already have provided an initial view of the complex landscape of somatic mutations in these tumors and some findings with important functional and clinical implications. This review addresses the major contributions and limitations of the microarray technologies in the understanding of lymphoid neoplasms and discusses how this knowledge may be transferred into the clinics. The initial results of the NGS studies are also presented.

Lymph Node Fine-Needle Cytology: Beyond Flow Cytometry

“…GEP has been conceived for the study of RNA and DNA changes, including chromosomal copy number alterations, genotyping and epigenetic modifications [60]. GEP platforms consist of numerous oligonucleotide probes immobilized on a solid surface, hybridized with DNA/RNA samples [60,61].…”

Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy

“…It brought great advances in cancer research and disclosed deregulated transcripts that are now being considered as prognostic or therapeutic biomarkers of neoplastic diseases (Sevov et al, 2012;Campo, 2013). Considering the availability of novel therapeutic possibilities for rare muscle disorders (Aartsma-Rus and Muntoni, 2013), finding prognostic biomarkers for disease severity or drug response will be of great benefit for patient care and treatment (Ferlini et al, 2013;Scotton et al, 2014).…”

Lymphoma classification and the tools of our trade: an introduction to the 2012 USCAP Long Course

“…Mutational analyses have perhaps been more important in the world of myeloid neoplasms up to this point; however, things are changing in that regard. While the ultimate technologies to be utilized remain to be established, as discussed by E Campo in this journal, 33 many discoveries are being made, particularly as whole genome/exome sequencing is being explored by many. [33][34][35][36][37] While for some entities, such as chronic lymphocytic leukemia, the mutations being discovered are each present in a relatively small proportion of cases, they may still be of great biological and clinical interest with therapeutic implications.…”

“…While the ultimate technologies to be utilized remain to be established, as discussed by E Campo in this journal, 33 many discoveries are being made, particularly as whole genome/exome sequencing is being explored by many. [33][34][35][36][37] While for some entities, such as chronic lymphocytic leukemia, the mutations being discovered are each present in a relatively small proportion of cases, they may still be of great biological and clinical interest with therapeutic implications. 33,[35][36][37] Detection of other mutations may be useful for diagnostic purposes, being present in a high proportion of a specific type of lymphoid neoplasm.…”

“…[33][34][35][36][37] While for some entities, such as chronic lymphocytic leukemia, the mutations being discovered are each present in a relatively small proportion of cases, they may still be of great biological and clinical interest with therapeutic implications. 33,[35][36][37] Detection of other mutations may be useful for diagnostic purposes, being present in a high proportion of a specific type of lymphoid neoplasm. For example, it has been learned only recently that hairy cell leukemia but very few other B-cell neoplasms have BRAF V600E mutations.…”