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Open AccessJournal ArticleDOI

The landscape of somatic copy-number alteration across human cancers

Rameen Beroukhim, +86 more
- 18 Feb 2010 - 
- Vol. 463, Iss: 7283, pp 899-905
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TLDR
It is demonstrated that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival, and a large majority of SCNAs identified in individual cancer types are present in several cancer types.
Abstract
A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.

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Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential

TL;DR: A hypothesis called the cancer gene island model is proposed, whereby gene islands encompassing high densities of STOP genes and low density of GO genes are hemizygously deleted to maximize proliferative fitness through cumulative haploinsufficiencies.
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Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer

TL;DR: A marked rewiring in the ceRNA program between normal and pathological breast tissue is documented by its “on/off” switch from normal to cancer, and vice-versa, which confers an interesting character to ceRNAs as potential oncosuppressive, or oncogenic, protagonists in cancer.
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Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis

TL;DR: It is shown that mitochondrial dysfunction—caused by defects in mitophagy—can promote the Warburg effect and tumor progression, and suggest better approaches to stratifying TNBC for treatment.
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The evolving war on cancer.

TL;DR: A paradigm shift in clinical research is poised to ensure that new molecular insights are rapidly applied to shape emerging cancer therapies, could this mark a turning point in the "War on Cancer"?
References
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Journal ArticleDOI

Controlling the false discovery rate: a practical and powerful approach to multiple testing

TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Roger E. McLendon, +233 more
- 23 Oct 2008 - 
TL;DR: The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
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The clonal evolution of tumor cell populations

TL;DR: Each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment, which should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
Journal ArticleDOI

In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector

TL;DR: The ability of HIV-based viral vectors to deliver genes in vivo into nondividing cells could increase the applicability of retroviral vectors in human gene therapy.
Journal ArticleDOI

Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection

TL;DR: A statistical model is proposed for the probe-level data, and model-based estimates for gene expression indexes are developed, which help to identify and handle cross-hybridizing probes and contaminating array regions.
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