RT Journal Article
SR Electronic
T1 Chromosomal Breakpoints in Primary Colon Cancer Cluster at Sites of Structural Variants in the Genome
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 1284
OP 1295
DO 10.1158/0008-5472.CAN-07-2864
VO 68
IS 5
A1 Camps, Jordi
A1 Grade, Marian
A1 Nguyen, Quang Tri
A1 Hörmann, Patrick
A1 Becker, Sandra
A1 Hummon, Amanda B.
A1 Rodriguez, Virginia
A1 Chandrasekharappa, Settara
A1 Chen, Yidong
A1 Difilippantonio, Michael J.
A1 Becker, Heinz
A1 Ghadimi, B. Michael
A1 Ried, Thomas
YR 2008
UL http://cancerres.aacrjournals.org/content/68/5/1284.abstract
AB Genomic aberrations on chromosome 8 are common in colon cancer, and are associated with lymph node and distant metastases as well as with disease susceptibility. This prompted us to generate a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array consisting of a tiling path of BAC clones. This analysis confirmed the dominant role of this chromosome. Unexpectedly, the position of the breakpoints suggested colocalization with structural variants in the human genome. In order to map these sites with increased resolution and to extend the analysis to the entire genome, we analyzed a subset of these tumors (n = 32) by comparative genomic hybridization on a 185K oligonucleotide array platform. Our comprehensive map of the colon cancer genome confirmed recurrent and specific low-level copy number changes of chromosomes 7, 8, 13, 18, and 20, and unveiled additional, novel sites of genomic imbalances including amplification of a histone gene cluster on chromosome 6p21.1-21.33 and deletions on chromosome 4q34-35. The systematic comparison of segments of copy number change with gene expression profiles showed that genomic imbalances directly affect average expression levels. Strikingly, we observed a significant association of chromosomal breakpoints with structural variants in the human genome: 41% of all copy number changes occurred at sites of such copy number variants (P < 2.2e−16). Such an association has not been previously described and reveals a yet underappreciated plasticity of the colon cancer genome; it also points to potential mechanisms for the induction of chromosomal breakage in cancer cells. [Cancer Res 2008;68(5):1284–95] ©2008 American Association for Cancer Research.