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CDCOCA: a statistical method to define complexity dependent co-occurring chromosomal aberrations
Genome Biology volume 11, Article number: P23 (2010)
Copy number alterations (CNA) play a key role in cancer development and progression. In general, more than one CNA can be detected in any given tumor; therefore co-occurring genetic CNA may point to co-operating cancer related genes. Existing methods for co-occurrence evaluation so far have not considered the overall heterogeneity of CNAs per tumor, resulting in a preferential detection of frequent changes with limited specificity for each association owing to the frequently high genetic instability of the samples.
We hypothesize that in cancer some linkage-independent CNAs might display a statistically non-random co-occurrence, and that these CNAs could be of pathogenetic relevance for the respective cancer. We also hypothesize that two CNAs co-occurring in samples with overall few changes (low complexity samples) represent a stronger association then coming from samples with a high number of changes. To verify our hypothesis, we here present a simulation based algorithm CDCOCA (complexity dependent co-occurring chromosomal aberrations). For an initial modeling approach, CNA data for bladder cancer and mantle cell lymphoma at cytogenetic band resolution was obtained from our Progenetix reference database (http://www.progenetix.net) and the CDCOCA was applied to them. A display of ~50 most frequent co-occurrences obtained after p value cut off along with selected cancer associated genes are shown here (Figure 1).
Our CDCOCA algorithm has constitutes a new approach to establish statistically significant co-occurring regional genomic imbalances from for example CGH data sets containing at least hundreds of individual copy number profiles. Along with finding CNAs from low/intermediate complexity samples, our algorithm points towards a generally low statistical specificity for co-occurrence of regional CNAs in a CNA rich samples, with a negative impact on pathway modeling approaches based on genomic copy number screening analyses derived from such data.
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Kumar, N., Rehrauer, H., Ca, H. et al. CDCOCA: a statistical method to define complexity dependent co-occurring chromosomal aberrations. Genome Biol 11, P23 (2010) doi:10.1186/gb-2010-11-s1-p23
- Mantle Cell Lymphoma
- Copy Number Alteration
- Cancer Related Gene
- Genomic Copy Number
- Genomic Imbalance