Article on the calculation of gene copy numbers published in Genome Biology
The article describes the calculation of gene copy numbers from array comparative hybridization (aCGH) data. The work originates from the Group for Molecular Radiation Biology at the Department of Radiation Biology.
The output from aCGH experiments gives relative values dependent on tumor cell fraction, experimental dynamics, etc., for the copy numbers, but the authors show in this work that absolute copy numbers as well as tumor cell fractions can be obtained from aCGH data as long as the DNA index (total DNA content in the individual tumor cells relative to normal cells) is known. (The DNA index is routinely measured by flow cytometry at The Radium Hospital.)
Furthermore, it was shown that tumor heterogeneity with respect to DNA copy numbers can be detected, and, sure enough, about 50% of the cervical carcinomas showed such heterogeneity. Possibly more surprising was the finding that about 20% of the Non-Hodgkins lymphomas also were heterogeneous.
Tumor heterogeneity in copy numbers indicates that the amplification/deletion of that region, presumably containing an oncogene/tumor suppressor gene, is a late event during carcinogenesis. In the heterogeneous cases it is thus possible to study certain aspects of tumor evolution from one single biopsy.
Links:
Lyng H, Lando M, Brovig RS, Svendsrud DH, Johansen M, Galteland E, Brustugun OT, Meza-Zepeda LA, Myklebost O, Kristensen GB, Hovig E, Stokke T.
GeneCount: Genome-wide calculation of absolute tumor DNA copy numbers from array CGH data. (link to PubMed)
Genome Biol. 2008 May 23;9(5):R86. [Epub ahead of print]
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