ABSTRACT
Introduction 332 Historical background: chromosomal aberrations in 333
lymphoid neoplasms A multistep model of lymphoid tumorigenesis 333 Types of chromosomal aberrations in lymphoid neoplasia 336 Balanced chromosomal aberrations: translocations, 337
inversions Unbalanced chromosomal aberrations associated 337
with gains of chromosomal material: trisomies, duplications, unbalanced translocations, amplifications, and complicons
Unbalanced chromosomal aberrations associated with 338 loss of chromosomal material: monosomies, deletions, and unbalanced translocations
Balanced chromosomal aberration with unbalanced 338 effect: uniparental disomy
Between chromosomes and DNA: epigenetic changes 338 in lymphoid neoplasms
Technical approaches to detect chromosomal aberrations 339 Conventional cytogenetic methods 340
Fluorescence in situ hybridization-based methods 340 Advanced fluorescence in situ hybridization-based 340
methods Array-based methods 340 Technical comparison 341 Molecular genetic methods 341 Future directions in diagnostic methods 342 Recurrent cytogenetic aberrations in lymphoid 342
malignancies – common themes Chromosomal translocations in lymphoid malignancies 343 Tumor suppressor genes in lymphoid malignancies 343 Gains and amplifications in lymphoid malignancies 344 Other forms of genetic instability in lymphoid 344
malignancies Inherited predispositions to B cell malignancies 345 The association of specific cytogenetic abnormalities 345
with specific subtypes of lymphoid malignancy Conclusions 346 Key points 347 References 347
Cancer is a genetic disease. All forms of malignancy are characterized by the presence of genetic abnormalities. Over and above point mutations at the level of DNA, gross changes at the chromosomal level can be detected in the vast majority of malignancies. By definition, these genetic aberrations are somatic in origin, and are thus not transmitted through the germ line. Many of these lesions are recurrent and are therefore considered to be pivotal to the pathogenesis of disease; in many instances, it is possible to confirm this hypothesis by recapitulating disease using mouse transgenic models that ‘knock in’ constructs that 1
This chapter is concerned with the description of the structural chromosomal lesions in lymphoid malignancies and their detection in routine clinical practice. These lesions have not only diagnostic but also prognostic and therapeutic applications and thus play an increasingly important role in patient management. The molecular origins and consequences of these lesions in terms of neoplastic transformation of normal B cells will be discussed elsewhere in this volume.
