@article{92821,
  author = {Tsafrir and Bacolod and Selvanayagam and Tsafrir and Shia and Zeng and Liu and Krier and RF Stengel and Francis Barany and WL Gerald and Phillip Paty and Domany and Daniel Notterman},
  title = {Relationship of gene expression and chromosomal abnormalities in colorectal cancer},
  abstract = { <p>Several studies have verified the existence of multiple chromosomal abnormalities in colon cancer. However, the relationships between DNA copy number and <span class="highlight">gene</span> expression have not been adequately explored nor globally monitored during the <span class="highlight">progression</span> of the <span class="highlight">disease</span>. In this work, three types of array-generated data (expression, single nucleotide polymorphism, and comparative genomic hybridization) were collected from a large set of colon cancer patients at various stages of the <span class="highlight">disease</span>. Probes were annotated to specific chromosomal locations and coordinated alterations in DNA copy number and transcription levels were revealed at specific positions. We show that across many large regions of the genome, changes in expression level are <span class="highlight">correlated</span> with alterations in DNA content. Often, large chromosomal segments, containing multiple genes, are transcriptionally affected in a coordinated way, and we show that the underlying mechanism is a corresponding change in DNA content. This implies that whereas specific chromosomal abnormalities may arise stochastically, the associated changes in expression of some or all of the affected genes are responsible for selecting cells bearing these abnormalities for clonal expansion. Indeed, particular chromosomal regions are frequently gained and overexpressed (e.g., 7p, 8q, 13q, and 20q) or lost and underexpressed (e.g., 1p, 4, 5q, 8p, 14q, 15q, and 18) in <span class="highlight">primary</span> colon tumors, making it likely that these changes favor tumorigenicity. Furthermore, we show that these aberrations are absent in normal colon mucosa, appear in benign adenomas (albeit only in a small fraction of the samples), become more frequent as <span class="highlight">disease</span> advances, and are found in the majority of metastatic samples.</p> },
  year = {2006},
  journal = {Cancer Research},
  volume = {66},
  pages = {2129-2137},
  month = {02/2006},
  url = {http://cancerres.aacrjournals.org/content/66/4/2129.long},
  language = {eng},
}