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This Week in Cancer Cell: Mar 30, 2012

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In Cancer Cell this week, researchers in the US and South Korea report that the ALK gene and the MYCN oncogene collaborate in the pathogenesis of neuroblastoma. The team generated a transgenic zebrafish model of neuroblastoma, and found that co-expression of activated ALK and MYCN triples the disease's penetrance and accelerates tumor onset. "MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and ultimately triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells," the team writes. "Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma."

Also in Cancer Cell this week, researchers in the US and Taiwan report an association between the mTOR and Hedgehog pathways in esophageal adenocarcinoma. The TNF-α/mTOR pathway is known to mediate the development of esophageal cancer, the team writes. Aberrant behavior in Gli1, a downstream effector of the Hedgehog pathway, has also been shown to be involved in this disease. For this study, the team found that "an activated mTOR/S6K1 pathway promotes Gli1 transcriptional activity and oncogenic function through S6K1-mediated Gli1 phosphorylation at Ser84, which releases Gli1 from its endogenous inhibitor, SuFu." Further, the team adds, "elimination of S6K1 activation by an mTOR pathway inhibitor enhances the killing effects of the HH pathway inhibitor." This suggests a rationale for combination therapies for esophageal adenocarcinoma that would affect both pathways.

Finally in Cancer Cell this week, researchers in the US and Europe describe the effect of transient low doses of DNA-demethylating agents like decitabine and azacitidine on hematological and epithelial tumor cells. "We show that transient exposure of cultured and primary leukemic and epithelial tumor cells to clinically relevant nanomolar doses, without causing immediate cytotoxicity, produce an antitumor memory response, including inhibition of subpopulations of cancer stem-like cells," the team writes. "These effects are accompanied by sustained decreases in genome-wide promoter DNA methylation, gene re-expression, and antitumor changes in key cellular regulatory pathways."

The Scan

Octopus Brain Complexity Linked to MicroRNA Expansions

Investigators saw microRNA gene expansions coinciding with complex brains when they analyzed certain cephalopod transcriptomes, as they report in Science Advances.

Study Tracks Outcomes in Children Born to Zika Virus-Infected Mothers

By following pregnancy outcomes for women with RT-PCR-confirmed Zika virus infections, researchers saw in Lancet Regional Health congenital abnormalities in roughly one-third of live-born children.

Team Presents Benchmark Study of RNA Classification Tools

With more than 135 transcriptomic datasets, researchers tested two dozen coding and non-coding RNA classification tools, establishing a set of potentially misclassified transcripts, as they report in Nucleic Acids Research.

Breast Cancer Risk Related to Pathogenic BRCA1 Mutation May Be Modified by Repeats

Several variable number tandem repeats appear to impact breast cancer risk and age at diagnosis in almost 350 individuals carrying a risky Ashkenazi Jewish BRCA1 founder mutation.