Purpose To determine Notch1 mutation status in oral squamous cell carcinoma (OSCC) from Chinese population and its potential clinical implications. Experimental Design Surgically resected OSCC tissues from 51 Chinese patients and 13 head and neck cancer (HNSCC) cell lines were sequenced for mutations in the entire coding regions of Notch1 and TP53 using a next-generation sequencing platform. Sequences of the genes were also determined in corresponding normal tissues from 46 of the 51 patients. Mutations and their association with clinical parameters were analyzed. Results Six mutations in Notch1 and 11 mutations in TP53 coding regions were detected in 4 (31%) and 10 (77%) of the 13 HNSCC cell lines, respectively. Forty-two somatic Notch1 mutations, including 7 nonsense mutations and 11 mutations within the domain commonly harboring potential activating mutations in ALL, were detected in 22 (43%) of the 51 Chinese OSCC tumors. In comparison, 25 somatic TP53 mutations were observed in 21 (41%) of the 51 tumors. Patients whose tumors carried Notch1 mutation had a significantly shorter overall and disease-free survivals (P=.004 and P=.001, respectively, by log-rank test) compared to those whose tumors carried no Notch1 mutation. Multivariate analysis showed that both Notch1 mutation and lymph node metastasis are independent prognostic factors in the patient population (P=.001). All 15 patients with both Notch1 mutation and nodal metastasis recurred or metastasized within 2 years after surgery. Conclusions Notch1 mutation is common in Chinese OSCC and associates with clinical outcomes. The complexity of the mutation spectrum warrants further investigation of Notch1 in Chinese patients with OSCC.

Snapdragon (Antirrhinum majus L.), a member of the Plantaginaceae family, is an important model for plant genetics and molecular studies on plant growth and development, transposon biology and self-incompatibility. Here we report a near-complete genome assembly of A. majus cultivar JI7 (A. majus cv.JI7) comprising 510 Megabases (Mb) of genomic sequence and containing 37,714 annotated protein-coding genes. Scaffolds covering 97.12% of the assembled genome were anchored on eight chromosomes. Comparative and evolutionary analyses revealed that a whole-genome duplication event occurred in the Plantaginaceae around 46–49 million years ago (Ma). We also uncovered the genetic architectures associated with complex traits such as flower asymmetry and self-incompatibility, identifying a unique duplication of TCP family genes dated to around 46–49 Ma and reconstructing a near-complete ψS-locus of roughly 2 Mb. The genome sequence obtained in this study not only provides a representative genome sequenced from the Plantaginaceae but also brings the popular plant model system of Antirrhinum into the genomic age.

Activation and recruitment of thermogenic cells in human white adipose tissues ("browning") can counteract obesity and associated metabolic disorders. However, quantifying the effects of therapeutic interventions on browning remains enigmatic. Here, we devise a computational tool, named ProFAT (profiling of fat tissue types), for quantifying the thermogenic potential of heterogeneous fat biopsies based on prediction of white and brown adipocyte content from raw gene expression datasets. ProFAT systematically integrates 103 mouse-fat-derived transcriptomes to identify unbiased and robust gene signatures of brown and white adipocytes. We validate ProFAT on 80 mouse and 97 human transcriptional profiles from 14 independent studies and correctly predict browning capacity upon various physiological and pharmacological stimuli. Our study represents the most exhaustive comparative analysis of public data on adipose biology toward quantification of browning after personalized medical intervention. ProFAT is freely available and should become increasingly powerful with the growing wealth of transcriptomics data.