Increasing genomic instability during premalignant neoplastic progression revealed through high resolution array-CGH

Lisa A. Lai, Thomas G. Paulson, Xiaohong Li, Carissa A. Sanchez, Carlo Maley, Robert D. Odze, Brian J. Reid, Peter S. Rabinovitch

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Chromosomal instability is regarded as an underlying mechanism of neoplastic progression, integral to the clonal selection and evolution that leads to cancer. We evaluated chromosomal instability in premalignant Barrett's esophagus tissue using high resolution Affymetrix mapping 100K SNP arrays as patients progressed through three molecular stages of disease - CDKN2A LOH only, CDKN2ALOH/TP53LOH, and CDKN2A LOH/TP53LOH with aneuploidy. Within individuals over time, we observed increases in both numbers and sizes of regions of LOH or copy number change. In the earliest CDKN2ALOH only samples, we detected few regions with both copy change and LOH, whereas copy loss and LOH were highly correlated in more advanced samples. These data indicate that genomic instability increases in severity and changes character during neoplastic progression. In addition, distinct patterns of clonal evolution could be discerned within a segment of Barrett's esophagus. Overall, this study illustrates that pre-malignant disease can be associated with extensive instability and clonal dynamics that evolve from an initial stage characterized by small recombination-based alterations to one with larger copy change events likely associated with mitotic instability.

Original languageEnglish (US)
Pages (from-to)532-542
Number of pages11
JournalGenes Chromosomes and Cancer
Volume46
Issue number6
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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    Lai, L. A., Paulson, T. G., Li, X., Sanchez, C. A., Maley, C., Odze, R. D., Reid, B. J., & Rabinovitch, P. S. (2007). Increasing genomic instability during premalignant neoplastic progression revealed through high resolution array-CGH. Genes Chromosomes and Cancer, 46(6), 532-542. https://doi.org/10.1002/gcc.20435