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Selected Articles from the February 1, 2009 Issue
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View the Table of Contents for the February 2009 issue of Molecular Cancer Research
Madhavan et al.
Page 157
Finding better therapies for the treatment of brain tumors is hampered by the lack of consistently obtained molecular data from disparate sources enabling translation of therapies from bench to bedside. Therefore, a critical factor in the advancement of biomedical research and clinical translation is the ease with which data can be integrated, redistributed, and analyzed both within and across functional domains. Madhavan and colleagues present Repository of Molecular Brain Neoplasia Data (Rembrandt), a cancer clinical genomics database and a Web-based data mining and analysis platform aimed at facilitating discovery by connecting the dots between clinical information and genomic characterization data.
Horne et al.
Page 199
The myelin and lymphocyte protein, MAL, has been implicated in the etiology of several human cancers. To gain an understanding of the role of MAL in breast cancer development, Horne and colleagues examined its transcriptional regulation and biological consequences both in vitro and clinically. The MAL promoter was frequently methylated in breast cancer, which correlated with transcriptional silencing. Furthermore, in breast cancer patients who did not receive chemotherapy, MAL expression was a significant predictive factor for disease-free survival. These data identify
MAL as a commonly altered gene in breast cancer with implications for response to chemotherapy.
Shi et al.
Page 230
Human pancreatic cancer commonly arises from pancreatic intraepithelial neoplasms or PanINs, and these are sometimes associated with acinar to ductal metaplasia (ADM) lesions. Shi and colleagues did careful laser capture microdissection to isolate each of these lesions and showed that
KRAS2 mutations can exist in ADM lesions, but only if the ADM is within the same lobule as a PanIN lesion, and in this case, the same
KRAS2 mutation is seen.
KRAS2 mutations do not exist in acinar cells within the same lobule or in isolated AMDs. These data firmly link PanINs with their associated ADMs, and this co-existence can be explained by two competing models, the linear progression model and the retrograde extension model.
REV1 is conserved among eukaryotes and is centrally involved in mutagenesis induced by common environmental carcinogens, including the cigarette smoke constituent benzo[a]pyrene (BP). The cellular function of this protein is thought to be involved in the recruitment of error-prone DNA polymerases to stalled replication forks, but its role in carcinogenesis has not been examined. This study shows that the level of REV1 could be reduced in the pulmonary epithelium of living mice using a hammerhead ribozyme delivered by a clinically available aerosol device. The study also shows that such a treatment is correlated with a reduction in the incidence and multiplicity of lung tumors. The data support the development of chemopreventive strategies using genetic approaches based on recent advances in the molecular mechanisms of mutagenesis.
