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The Sunday Papers (20 August '06 edition)

Knight et al.
Unraveling adaptive evolution: how a single point mutation affects the protein coregulation network

Carter et al.
A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers

Burdick et al.
In silico method for determining genotypes in pedigrees

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CIN profile in glioma seems to be associated with tumor grade
Both glioma datasets presented in the paper (Phillips & Freije) include grade 3 and grade 4 gliomas. Grade 4 gliomas are known to have poor survival. Most of the samples in which the CIN25 signature is high are grade 4 (*). Thus, the CIN25 signature partially separates grade 3 from grade 4. When repeating the analysis (for both Phillips & Freije datasets), but separately for each grade, the CIN25 signature does not divide the samples into groups with significant survival differences. The same is observed for the Rich dataset, another public glioma dataset composed of grade 4 tumors only.
Tumor grading for glioma comprises in part proliferation. As mentioned in the Carter paper, the CIN25 signature partially overlaps with the proliferation signature. This may be the reason why significance is lost when correcting for grading. While other tumor types are characterized by grading and staging, where grading represents the morphology of the malignancy, and staging - the invasiveness (including metastasis), brain tumors have only grading.

* Repeating the analysis as described in the supplementary methods but using standard RMA normalization:
Freije dataset
Low CIN25 - 19 Grade 3 and 28 Grade 4 patients
High CIN25 - 7 Grade 3 and 31 Grade 4

Phillips dataset
Low CIN25 - 16 Grade 3 and 24 Grade 4
High CIN25 - 5 Grade 3 and 27 Grade 4

Tal Shay, Monika E. Hegi, Eytan Domany
From the Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel (T.S. and E.D.) and the Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University Hospital Lausanne, Lausanne, Switzerland (M.E.H.)

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