A genome sequencing study published online in Cell by researchers from Massachusetts provides a peek at the processes behind small-cell lung carcinoma development and progression. The team developed a genetically engineered mouse model of the small-cell lung carcinoma missing two of the genes that have previously been shown to be oft-mutated in human forms of the disease. By sequencing the genomes or exomes of primary or metastatic tumors that developed in six of the mice, together with matched normal tissue sample, the investigators narrowed in on recurrent copy number changes, rearrangements, and somatic mutations in the mouse models of small-cell lung carcinoma. They also tracked down patterns associated with metastasis, including sequential alterations in tumors that spread to other parts of the body.
Another Cell study suggests synonymous genetic mutations that don't alter the resulting amino acid sequence of a protein can still play a driving role in human cancer development. Spanish researchers scrutinized protein-coding sequences from thousands of cancer samples in their effort to study these supposedly silent mutations. Results from the analyses indicated that somatic, synonymous mutations are over-represented in known oncogenes and appear to be subject to selection in a manner that varies with the type of cancer involved.
A team from the Netherlands, Germany, and the US explore the consequences of chromosomal rearrangements that contribute to acute myeloid leukemia development but do not create gene fusions. Using functional genomics and genome engineering approach, the researchers focused on rearrangements involving sections of chromosome 3 that have been implicated in unusual EVI1 regulatory gene expression. Their results suggest that such rearrangements alter the position of enhancer elements normally found near the GATA2 gene, leading to a bump in expression of EVI1, a stem cell regulator. "Our data show that structural rearrangements involving the chromosomal repositioning of a single enhancer can cause deregulation of two unrelated distal genes, with cancer as an outcome."