American Association for Cancer Research

February 1 Cancer Research Highlights

PDF Version for Printing pdf4.gif

Selected Articles from the February 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 February 1 issue of Cancer Research.


Pervasive Divergence of FL Methylome

Killian et al.

Page 758

Killian et al.Emerging technologies allow broad profiling of the cancer genome for differential DNA methylation relative to benign cells. Killian and colleagues describe a robust method for differentially methylated target (DMT) discovery in archival pathology samples dating back over 10 years. Evaluation of matched formalin-fixed, paraffin-embedded and frozen surgical pathology replicates demonstrated equivalent recovery of the cancer methylome from differently archived tissue specimens. Comparison of lymph nodes with reactive hyperplasia versus follicular lymphoma (FL) identified hundreds of DMTs distributed among 183 unique genes in FL. Integrated gene expression and DNA methylation analysis is consistent with a pervasive epigenomic remodeling process in FL that, strikingly, affects predominantly nonlymphoid genes. 
 

CDK6 in Thymocyte Development and Tumorigenesis

Hu et al.

Page 810

Cyclins and cyclin-dependent kinases (cdks) that control the G1-S phase transition are important regulators of differentiation in specific tissues. Frequently, tumorigenesis dependent on deregulated cdk function reflects this tissue specificity. Elimination of CDK6, a partner of the D-type cyclins, has been shown to result in pronounced thymic atrophy due to reduced thymocyte numbers. Hu and colleagues used the OP9-DL1 thymic stroma mimetic to show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation in cell culture. Further, mice lacking CDK6 are highly resistant to the development of AKT-dependent thymic lymphoma. Both phenotypes may result from defects in differentiation steps prior to the DN3-to-DN4 transition. These results provide evidence of a key role for CDK6 in differentiation that is exploited in T-cell lymphomagenesis, and suggest that CDK6 may be a potential therapeutic target in this disease.


Red and Processed Meats, Meat Mutagens, and Lung Cancer

Lam et al.

Page 932

Lung cancer is the leading cancer-related cause of death worldwide and cigarette smoking is the primary risk factor. Lam and colleagues found that high intake of fresh red meats, processed meats, and exposure to meat-mutagens formed during high cooking temperatures increased the risk of lung cancer, based on the analysis of approximately 4,000 individuals from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. The risks were strongest amongst never smokers and restricted to the adenocarcinoma and squamous cell carcinoma subtypes. Consumption of red meats and cooking-related mutagens may be preventable risk factors in the etiology of lung cancer.


Hypoxic tumor cells are likely to be resistant to conventional chemotherapy, in large part because many anticancer drugs are unable to penetrate into poorly oxygenated tumor tissue. Trédan and colleagues describe the selective localization of the bioreductive prodrug AQ4N in hypoxic tumor regions and show that it complements the limited distribution of the related anticancer drug mitoxantrone. Whereas mitoxantrone is taken up by proximal cells and penetrates slowly, AQ4N rapidly penetrates tumor tissue and accumulates in hypoxic regions. These results describe a promising strategy to overcome chemoresistance due to the limited distribution of conventional anticancer agents. 


Integrative Genomics for Lung Cancer Prediction

Broët et al.

Page 1055

Broet et al.Identifying high-risk patients most likely to benefit from adjuvant treatment remains an important challenge in early non–small-cell lung cancer (NSCLC). Broët and colleagues identified copy number alterations linked to survival from a series of 85 stage IB NSCLC patient samples. The authors then selected genes within these regions exhibiting copy number–driven expression to construct a novel integrated signature (IS) and found that the IS predicted clinical outcome in this series as well as in two additional independent stage I NSCLC cohorts. These results suggest that recurrent copy number alterations, when combined with gene expression information, can be successfully used to create robust predictors of clinical outcome in early-stage NSCLC. 


Top