Patterns of Chromosomal Aberrations in Solid Tumors

Abstract

Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality.

Keywords: Chromosomal aberrations; Colorectal cancer; Copy number alterations; Gene expression; Genomic imbalances; Molecular cytogenetic; Ploidy; Solid tumors.

Fig. 1

Schematic illustration of commonly observed numerical and structural chromosome alterations identified in solid tumors, and the methodologies capable of their detection. Detection of an alteration, however, is not necessarily synonymous with the ability to unambiguously determine the genomic origin of aberrant material. Chromosome banding, SKY/M-FISH and chromosome comparative genomic hybridization (CGH) are low resolution techniques, whereas array-based CGH (aCGH), single nucleotide polymorphism (SNP) arrays and next-generation sequencing (NGS) are much higher resolution methodologies. (Adapted from Albertson et al. 2003)

Fig. 2

Progression model of colorectal carcinogenesis. The progression of low-grade adenomas to high-grade adenomas is accompanied by gains of chromosomes 7 and 20q. Gains of chromosomes 8q and 13, as well as losses of chromosomes 4p, 8p and 18q, indicate transition into invasive carcinomas. These chromosomal aberrations, which are specific for colorectal cancer, accompany the genetic (mutational) changes observed at the level of individual genes that serve as the basis for the colorectal cancer progression model, referred to as the adenoma-carcinoma-sequence by Vogelstein and Fearon

Fig. 3

Diagram of genomic profiles showing the most common gains and losses in colon, rectal, head and neck, bladder and breast cancer. Note the prevalence of specific genomic imbalances unique to each tumor type, thus illustrating the individual landscapes of copy number alterations. SNP array data were collected from The Cancer Genome Atlas (http://cancergenome.nih.gov/)

Fig. 4

Plot showing the correlation between copy number changes and gene expression from a set of colorectal cancers. In yellow, genomic segments that are copy number neutral; in red, genomic segments that show a copy number reduction; and in green, genomic segments that show a copy number gain. The Y-axis indicates the levels of gene expression in log₂ ratio. (Adapted from Ried et al. 2012)