Acquired Chromosomal Abnormalities and Their Potential Formation Mechanisms in Solid Tumours

Abstract

Solid tumours include numerous malign or relatively less benign types of carcinomas and sarcomas. Acquired chromosomal abnormalities in solid tumours are hallmarks of gene deregulation and genome instability. Chromosomal abnormalities are mainly classified into two groups: structural and numerical alterations. Structural rearrangements involve chromosomal aberrations such as deletion, translocation, duplication, inversion and gene amplification, whereas numerical abnormalities result in aneuploidy or polyploidy. Structural chromosome abnormalities can arise from non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ) and fork stalling and template switching (FoSTeS). Numerical abnormalities can form through various errors in the mitotic spindle checkpoint and some cellular processes during mitosis. This chapter reviews acquired structural and numerical chromosomal abnormalities in solid tumours and presents potential formation mechanisms. In this chapter, the relationship between long inverted repeats (LIRs) and MYCN amplification in neuroblastoma was also investigated. The distribution of LIRs was determined at chromosome 2p25.3-2p24.3, using inverted repeat finder (IRF) software. LIRs were also identified at boundaries of amplicons in 14 neuroblastoma cell lines and 42 solid tumours, involving MYCN amplification. Statistical analysis showed a significant association between LIRs and MYCN amplification loci. Present data provide important insights into MYCN amplification mechanism. Therefore, a new model mechanism for formation of the MYCN amplification is proposed at the end of the chapter.