Research

A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

Eike Staub^1,11* , Jörn Gröne^2* , Detlev Mennerich^5,8 , Stefan Röpcke^1,11 , Irina Klamann⁴ , Bernd Hinzmann³ , Esmeralda Castanos-Velez³ , Benno Mann⁷ , Christian Pilarsky⁶ , Thomas Brümmendorf^8,9 , Birgit Weber^8,10 , Heinz-Johannes Buhr² and André Rosenthal³

¹  Max Planck Institute for Molecular Genetics, Dept. of Computational Molecular Biology., Berlin, Germany

²  Dept. of General, Vascular and Thoracic Surgery, Charité – Campus Benjamin Franklin, Berlin, Germany

³  Signature Diagnostics AG, Potsdam, Germany

⁴  HELIOS Hospital Emil von Behring, Institute of Pathology, Berlin, Germany

⁵  Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany

⁶  Dept. of Visceral, Thoracic, and Vascular Surgery, University Hospital Carl Gustav Carus Dresden, Germany

⁷  Department of Surgery, Augusta-Kranken-Anstalt GmbH, Bochum, Germany

⁸  metaGen Pharmaceuticals i.L., Berlin, Germany

⁹  Present address: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland

¹⁰  Present address: immatics biotechnologies GmbH, Tübingen, Germany

¹¹  Present address: ALTANA Pharma AG, Preclinical Research Bioinformatics, Konstanz, Germany

author email corresponding author email* Contributed equally

Molecular Cancer 2006, 5:37doi:10.1186/1476-4598-5-37

Published:	18 September 2006

Abstract

Background

Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression.

Results

We investigated genome-wide gene expression in colorectal carcinoma (CRC) and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes) are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC.

Conclusion

An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin) also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.