December 1 Cancer Research Highlights

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Selected Articles from the December 1, 2007 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the December 1 issue of Cancer Research.

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FANC/BRCA Mutants Hypersensitive to Formaldehyde

Ridpath et al.

Page 11117

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High Plasma Cysteinylglycine Associated with Higher Breast Cancer Risk

Lin et al.

Page 11123

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Common Variants Play Important Roles in Colorectal Cancer Risk

Poynter et al.

Page 11128

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Novel Germ Line NBS1 Mutation with Functional Significance

Ebi et al.

Page 11158

The Nijmegen Breakage Syndrome 1 protein (NBS1) is crucial for maintaining genomic stability and occurs in a protein complex at sites of DNA double strand breaks. Ebi and co-investigators identified an unprecedented type of heterozygous germ line NBS1 mutant termed NBS1 IVS11+2insT. This protein is profoundly defective in binding to MRE11 and other DNA damage response proteins and the mutant demonstrated impaired ATM phosphorylation in response to low-dose irradiation. In screening 1,743 patients with various cancers and 2,348 control subjects, the presence of the heterozygous IVS11+2insT mutation appeared to confer an increased risk for gastrointestinal cancers in select populations. The IVS11+2insT mutant may confer an increased risk for the development of certain types of common cancers.  

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Aurora-A Kinase Modulates BRCA1 Regulation of Centrosomes

Sankaran et al.

Page 11186

The breast and ovarian cancer–specific tumor suppressor BRCA1 regulates the function of centrosomes in breast cells. Sankaran and colleagues observed that BRCA1-dependent inhibition of centrosome function was high in S phase but significantly lower during mitosis. The cell cycle–specific effects of BRCA1 on centrosome function were detected in living cells and in cell-free experiments using centrosomes purified from cells at specific stages of the cell cycle. The authors show that Aurora-A kinase modulates the BRCA1 inhibition of centrosome function by decreasing the E3 ubiquitin ligase activity of BRCA1. 

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Variation in the Tyrosine Kinome of Commonly Used Cancer Cell Lines

Ruhe et al.

Page 11368

Targeting the cancer kinome has been established as a highly promising mode of therapeutics. To comprehensively examine the cancer kinome for genetic variations in expressed protein tyrosine kinases, Ruhe and colleagues conducted a sequence analysis of the entire tyrosine kinase transcriptome of 254 established tumor cell lines. Somatic mutations and polymorphisms with potential functional and clinical relevance were identified, and hints for broader application to the spectrum of currently used cancer therapeutics were provided. The cell line–specific profiles of tyrosine kinase variants established in this survey may define cell line–specific signalling cascades and aid in the design and interpretation of cell line–based cancer studies.

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