Researchers in China and the US describe recurrent alterations that inactive the mTORC1 signaling pathway gene DEPDC5 in gastrointestinal stromal tumors (GISTs), consistent with a potential tumor suppressor role for the gene. The team did exome sequencing on matched tumor and normal samples from 40 individuals with GIST, uncovering previously identified activating mutations in receptor tyrosine kinase genes such as KIT, along with the recurrent changes inactivating DEPDC5. The DEPDC5 changes turned up in seven of the original 40 tumors, the authors report, and two of the 15 GIST validation set tumors. Their follow up analyses in vitro and in mouse models suggest DEPDC5 inactivation boosts cell proliferation and aggressiveness. Such results "explain, in part, the non-uniform response to KIT [tyrosine kinase inhibitor (TKI)] treatment observed in KIT-mutant GIST patients and provide a rationale for testing an mTOR inhibitor in combination with a KIT TKI in KIT-mutant GIST patients," they write.
A team from Panama, the US, and Taiwan explores the taxonomic reliability of sequences in the GenBank database, reasoning that biodiversity research is increasingly informed by environmental DNA sequencing and GenBank. Based on their analyses of more than 4.7 million GenBank sequences representing more than a dozen protein-coding mitochondrial genes from metazoan animals, the researchers suggest sequence mislabeling and larger taxonomic errors are relatively rare in the database. "Our encouraging results suggest that the rapid uptake of DNA-based approaches is supported by a bioinformatic infrastructure capable of assessing both the losses to biodiversity caused by global change and the effectiveness of conservation efforts aimed at slowing or reversing these losses," they write.
Spanish investigators look at the consequences of tumor suppressor gene inactivation in high-grade neuroendocrine forms of lung cancer, particularly large-cell neuroendocrine cell carcinoma (LCNEC) and small-cell lung carcinomas (SCLC). The team established a mouse model of LCNEC by simultaneously dialing down four tumor suppressor genes — RB1, RBL1, PTEN, and TP53 — in mouse lung epithelial cells. It also came up with a mouse model of SCLC by muting the same tumor suppressor set in basal cells. "Molecular and transcriptomic analyses of both models revealed strong similarities to their human counterparts," the authors report, noting that they were able to follow disease progression with a molecular imaging strategy known as Ga-DOTATOC.