Cancer chromosomal instability: therapeutic and diagnostic challenges

• Published in: EMBO reports Vol. 13; no. 6; pp. 528 - 538
• Main Authors: McGranahan, Nicholas, Burrell, Rebecca A, Endesfelder, David, Novelli, Marco R, Swanton, Charles
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-06-2012; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Adaptations; Aneuploidy; Animals; Cancer; Chromosomal Instability; Chromosome Segregation; Chromosomes; Drug resistance; Ecological adaptation; Evolution; Genomic instability; Genomics; Heterogeneity; Humans; intra-tumour heterogeneity; Karyotyping; Molecular Diagnostic Techniques; Molecular Targeted Therapy; Neoplasms - diagnosis; Neoplasms - drug therapy; Neoplasms - genetics; Prognosis; Review; Risk assessment; Tumors
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2012.61

Chromosomal instability (CIN)—which is a high rate of loss or gain of whole or parts of chromosomes—is a characteristic of most human cancers and a cause of tumour aneuploidy and intra‐tumour heterogeneity. CIN is associated with poor patient outcome and drug resistance, which could be mediated by evolutionary adaptation fostered by intra‐tumour heterogeneity. In this review, we discuss the clinical consequences of CIN and the challenges inherent to its measurement in tumour specimens. The relationship between CIN and prognosis supports assessment of CIN status in the clinical setting and suggests that stratifying tumours according to levels of CIN could facilitate clinical risk assessment.
This review provides a much‐needed translational perspective into the issue of aneuploidy and chromosomal instability, discussing the prognostic value of CIN assessment in human tumours, methods to analyze it and how it could be therapeutically targeted.