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This Week in the Journal of the National Cancer Institute: Jul 1, 2011

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In the Journal of the National Cancer Institute this week, researchers in Canada present findings from a study of the tumor characteristics associated with mammographic detection of breast cancer. The team conducted a study of 431,480 women screened for breast cancer between January 1994 and December 2002 — it found that interval cancers diagnosed within 24 months after a negative mammogram were of a higher stage and grade than matched breast cancers detected by a screen. "True interval cancers were more likely to have additional adverse prognostic features of estrogen and progesterone receptor negativity and nonductal morphology," the researchers write. "The findings suggest a need for more sensitive screening modalities to detect true interval breast cancers and different approaches for early detection of fast-growing tumors."

Also in the Journal of the National Cancer Institute this week, US researchers use high-throughput screening to identify an inhibitor of the EWS-FLI1 oncogenic transcription factor. Continued expression of EWS-FLI1 is believed to be critical for cell survival in Ewing sarcoma family tumors, and because it is a transcription factor, it is thought the be undruggable, the researchers write. However, the team developed a high-throughput screen to evaluate the effects of more than 50,000 compounds on EWS-FLI1 activity, and found that the compound "mithramycin inhibited expression of EWS-FLI1 downstream targets at the mRNA and protein levels and decreased the growth of Ewing sarcoma family tumor cells" both in vitro and in vivo.

And finally in the Journal of the National Cancer Institute this week, researchers in Europe have identified SDHA loss-of-function mutations in KIT–PDGFRA wild-type gastrointestinal stromal tumors using massively parallel sequencing. The team sequenced the tumor transcriptome of two young adult patients with sporadic KIT/PDGFRA wild-type gastrointestinal stromal tumors, and found that the only disease-related variants were in SDHA. "This is the first report, to our knowledge, that identifies SDHA inactivation as a common oncogenic event in gastrointestinal stromal tumors that lack a mutation in KIT and PDGFRA," the authors write.

The Scan

Genome Sequences Reveal Range Mutations in Induced Pluripotent Stem Cells

Researchers in Nature Genetics detect somatic mutation variation across iPSCs generated from blood or skin fibroblast cell sources, along with selection for BCOR gene mutations.

Researchers Reprogram Plant Roots With Synthetic Genetic Circuit Strategy

Root gene expression was altered with the help of genetic circuits built around a series of synthetic transcriptional regulators in the Nicotiana benthamiana plant in a Science paper.

Infectious Disease Tracking Study Compares Genome Sequencing Approaches

Researchers in BMC Genomics see advantages for capture-based Illumina sequencing and amplicon-based sequencing on the Nanopore instrument, depending on the situation or samples available.

LINE-1 Linked to Premature Aging Conditions

Researchers report in Science Translational Medicine that the accumulation of LINE-1 RNA contributes to premature aging conditions and that symptoms can be improved by targeting them.