American Association for Cancer Research

April 1 Cancer Research Highlights

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Selected Articles from the April 1, 2009 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 April 1 issue of Cancer Research.


Novel Prostate Cancer Risk Locus at 19q13

Hsu et al.

Page 2720

Hsu and colleagues identified two candidate single nucleotide polymorphisms (SNPs) associated with prostate cancer risk by examining results from a genome-wide association study of prostate cancer from the Cancer Genetic Markers of Susceptibility (CGEMS) initiative and a population-based case-control study in Sweden (CAPS). Further examination of these two SNPs in additional prostate cancer cases and controls from CAPS and Johns Hopkins Hospital confirmed one SNP. Altogether, the frequency of the risk allele of rs887391 at 19q13 was consistently higher in cases than controls among each of seven study populations examined from a combined allelic test (P = 3.2 x 10−7).  
 

Breast Cancer Risk Haplotype in the Caspase-8 Gene

Shephard et al.

Page 2724

A polymorphic variant in the caspase-8 (CASP8) gene, D302H, was recently confirmed to be associated with breast cancer risk. However, the functional impact of this polymorphism, if any, is not yet clear, and it is likely that other variants in or around the CASP8 gene are also important in breast cancer susceptibility. Shephard and colleagues genotyped a panel of tagging SNPs spanning the gene and identified a four-SNP CASP8 haplotype more strongly associated with breast cancer than any individual SNP. This risk haplotype is likely to carry one or more underlying breast cancer susceptibility alleles. An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer.


Immune-Induced Generation of Breast Cancer Stem Cells

Santisteban et al.

Page 2887

The breast cancer stem cell (BCSC) hypothesis suggests that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source is unclear.  Santisteban and colleagues demonstrate that in vivo epithelial to mesenchymal transition (EMT) induced by CD8 T cells results in tumors with characteristics of BCSCs including potent tumorigenicity, ability to re-establish an epithelial tumor, and enhanced resistance to drugs and radiation. In contrast to the hierarchal cancer stem cell hypothesis, their results show that EMT can produce the BCSC phenotype. These findings have several important implications for disease progression and relapse, as well as advancing our understanding of the BCSC biology so these cells can be eradicated.


Nishijo et al.The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcomas of childhood; yet it is difficult to cure when metastatic despite over 35 years of cooperative trials. Nishijo and colleagues show that a genetically engineered mouse model of ARMS shares the natural history and pathological features of the human disease. The authors also show that the pathognomonic, translocation-mediated Pax3:Fkhr fusion gene is overexpressed relatively late in disease progression. With an eye toward therapeutics, the authors employ a cross-species analysis not only to define a Pax3:Fkhr gene expression signature, but also to identify potential targets of molecular therapeutics.  


Genetic Effects on Cancers of the Upper Aerodigestive Tract

Canova et al.

Page 2956

Cancers of the upper aerodigestive tract (UADT) account for about 10% of cancers worldwide and 6% of all new cancers in Europe. Canova and colleagues analyzed 115 single nucleotide polymorphisms (SNPs) from 62 a priori–selected genes from patient samples obtained from the ARCAGE study, which includes 10 European countries comprising 1,500 UADT cases and 1,500 controls. Notable results (P trend < 0.01) were identified for SNPs in CYP2A6, MDM2, TNF, and GASC1, pointing to potentially relevant pathways for these cancers. Additional detailed characterization of these pathways, as well as more detailed genome-wide studies of head and neck cancer, will elucidate the genetic susceptibility of these cancers.


CD47 in Bone Biology and Bone Metastasis

Uluçkan et al.

Page 3196

Uluçkan et al.CD47 is an atypical member of the immunoglobulin superfamily that interacts with and activates β3 integrins. β3 integrin–/–  mice are protected from bone metastasis, but the role of CD47 in skeletal homeostasis and bone metastasis is not known. Uluçkan and colleagues report that CD47–/–  mice had increased bone mass and defective osteoclast function in vivo, with high doses of RANKL and inhibition of nitric oxide synthase rescuing the defect. In a model of tumor metastasis to bone, bone tumor burden was decreased in the CD47–/– mice compared to wild-type controls. These data demonstrate that CD47 regulates osteoclastogenesis, in part, via regulation of nitric oxide production, and its disruption leads to a decrease in tumor bone metastasis. 

 


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