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This Week in the Journal of the National Cancer Institute: May 31, 2012


In the Journal of the National Cancer Institute, researchers in Japan report on the effect of ADAM28 on carcinoma cell metastasis. Using a yeast two-hybrid system, the researchers screened the human lung cDNA library for ADAM28-binding proteins and uncovered von Willebrand factor as a potential target of ADAM28. They examined exogenous VWF-induced apoptosis and ADAM28 expression in several human cancer cell lines, including lung, breast, renal cell, and liver as well as in mouse models. They found that ADAM28 could bind to and cleave native VWF, and that cells with low ADAM28 expression were susceptible to VWF-induced apoptosis, while cells with high ADAM28 expression were resistant. "Knockdown of ADAM28 expression in PC-9 and MDA-MB231 [lung cancer] cells by shRNA showed increased carcinoma cell apoptosis mainly in lung blood vessels and statistically significantly decreased lung metastasis at week 3 after injection," the team writes. "Similar inhibition of lung metastasis was observed with ADAM28-siRNA and anti-ADAM28 antibody." This shows that ADAM28 cleaves pro-apoptotic VWF, and enhances lung metastasis.

Also in the Journal of the National Cancer Institute, researchers in the US and Europe report on the role of tripartite motif family protein 27 in the development of cancer. Using cancer profiling arrays containing paired tumor and normal cRNA and murine models of skin cancer, the team studied TRIM27 expression and found that levels of TRIM27 transcripts are statistically significantly increased in common human cancers like colon and lung, compared to normal tissues. Additionally, mice with disrupted expression of murine TRIM27 were resistant to chemically induced skin cancer, compared to their wildtype littermates, the team says. "TRIM27 expression is a modifier of disease incidence and progression relevant to the development of common human cancers and is a potential target for intervention in cancer," the authors write.

The Scan

Lung Cancer Response to Checkpoint Inhibitors Reflected in Circulating Tumor DNA

In non-small cell lung cancer patients, researchers find in JCO Precision Oncology that survival benefits after immune checkpoint blockade coincide with a dip in ctDNA levels.

Study Reviews Family, Provider Responses to Rapid Whole-Genome Sequencing Follow-up

Investigators identified in the European Journal of Human Genetics variable follow-up practices after rapid whole-genome sequencing.

BMI-Related Variants Show Age-Related Stability in UK Biobank Participants

Researchers followed body mass index variant stability with genomic structural equation modeling and genome-wide association studies of 40- to 72-year olds in PLOS Genetics.

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.