Combining chromosomal arm status and significantly aberrant genomic locations reveals new cancer subtypes.

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Version: Final published version
Serval ID
serval:BIB_DB22060CD031
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Combining chromosomal arm status and significantly aberrant genomic locations reveals new cancer subtypes.
Journal
Cancer Informatics
Author(s)
Shay T., Lambiv W.L., Reiner-Benaim A., Hegi M.E., Domany E.
ISSN
1176-9351[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
7
Pages
91-104
Language
english
Abstract
Many types of tumors exhibit characteristic chromosomal losses or gains, as well as local amplifications and deletions. Within any given tumor type, sample specific amplifications and deletions are also observed. Typically, a region that is aberrant in more tumors, or whose copy number change is stronger, would be considered as a more promising candidate to be biologically relevant to cancer. We sought for an intuitive method to define such aberrations and prioritize them. We define V, the "volume" associated with an aberration, as the product of three factors: (a) fraction of patients with the aberration, (b) the aberration's length and (c) its amplitude. Our algorithm compares the values of V derived from the real data to a null distribution obtained by permutations, and yields the statistical significance (p-value) of the measured value of V. We detected genetic locations that were significantly aberrant, and combine them with chromosomal arm status (gain/loss) to create a succinct fingerprint of the tumor genome. This genomic fingerprint is used to visualize the tumors, highlighting events that are co-occurring or mutually exclusive. We apply the method on three different public array CGH datasets of Medulloblastoma and Neuroblastoma, and demonstrate its ability to detect chromosomal regions that were known to be altered in the tested cancer types, as well as to suggest new genomic locations to be tested. We identified a potential new subtype of Medulloblastoma, which is analogous to Neuroblastoma type 1.
Keywords
Array CGH, Amplifications, Deletions, Medulloblastoma, Neuroblastoma
Pubmed
Create date
29/01/2009 19:08
Last modification date
20/08/2019 16:00
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