nature biotechnology advance online publication l e t t e r sThe brown planthopper (BPH) is the most destructive pest of rice (Oryza sativa) and a substantial threat to rice production, causing losses of billions of dollars annually 1,2 . Breeding of resistant cultivars is currently hampered by the rapid breakdown of BPH resistance 2 . Thus, there is an urgent need to identify more effective BPH-resistance genes. Here, we report molecular cloning and characterization of Bph3, a locus in rice identified more than 30 years ago that confers resistance to BPH. We show that Bph3 is a cluster of three genes encoding plasma membrane-localized lectin receptor kinases (OsLecRK1-OsLecRK3). Introgression of Bph3 into susceptible rice varieties by transgenic or marker-assisted selection strategies significantly enhanced resistance to both the BPH and the white back planthopper. Our results suggest that these lectin receptor kinase genes function together to confer broad-spectrum and durable insect resistance and provide a resource for molecular breeding of insect-resistant rice cultivars.BPH (Nilaparvata lugens Stål, Hemiptera, Delphacidae) is a monophagous, phloem-sucking herbivore. It sucks the sap from the rice phloem using its stylet, and causes direct damage to rice plants. BPH can also cause indirect damage to rice plants through the transmission of viruses including the rice ragged stunt virus and grassy stunt virus 2 . Repeated overapplication of pesticides for BPH management has heavily polluted the environment 3 . Breeding of resistant cultivars is the most cost-effective and environmentally responsible strategy for BPH management but developing insect resistant cultivars by traditional breeding approaches is extremely difficult and time consuming owing to a paucity of knowledge about BPH resistance genes and germplasm.To date, 28 BPH resistance loci have been identified from cultivated and wild species of Oryza 2,4,5 . Only two of these resistance genes, Bph14 and Bph26 have been cloned to date 6,7 . In addition, BPH resistance of IR26 and IR36, two widely cultivated rice varieties that harbor the BPH resistance loci Bph1 and bph2, respectively, was quickly broken down in just a few years owing to the rapid adaptation of the BPH 8 . Thus, there is still an urgent need to identify new types of resistance genes and germplasm for developing efficient approaches to breed broad-spectrum and durable BPH-resistant rice cultivars. Notably, the Bph3 locus, originally identified in the Sri Lankan indica cultivar Rathu Heenati 9 , displayed resistance to four BPH biotypes (BPH biotypes refer to specific populations of BPH classified according to their virulence on different BPH resistance genes) 2,10 . Furthermore, rice varieties harboring Bph3 deployed more than 30 years ago in the Philippines are still resistant to BPH 8 . However, the molecular basis of this broad-spectrum and durable resistance of Bph3 against BPH remains unknown.We observed that Bph3-containing Rathu Heenati infested with BPH of mixed biotypes (biotype ...

BackgroundCharacterisation of colorectal cancer (CRC) genomes by next-generation sequencing has led to the discovery of novel recurrently mutated genes. Nevertheless, genomic data has not yet been used for CRC prognostication.ObjectiveTo identify recurrent somatic mutations with prognostic significance in patients with CRC.MethodExome sequencing was performed to identify somatic mutations in tumour tissues of 22 patients with CRC, followed by validation of 187 recurrent and pathway-related genes using targeted capture sequencing in additional 160 cases.ResultsSeven significantly mutated genes, including four reported (APC, TP53, KRAS and SMAD4) and three novel recurrently mutated genes (CDH10, FAT4 and DOCK2), exhibited high mutation prevalence (6–14% for novel cancer genes) and higher-than-expected number of non-silent mutations in our CRC cohort. For prognostication, a five-gene-signature (CDH10, COL6A3, SMAD4, TMEM132D, VCAN) was devised, in which mutation(s) in one or more of these genes was significantly associated with better overall survival independent of tumor-node-metastasis (TNM) staging. The median survival time was 80.4 months in the mutant group versus 42.4 months in the wild type group (p=0.0051). The prognostic significance of this signature was successfully verified using the data set from the Cancer Genome Atlas study.ConclusionsThe application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of TNM staging.

Brown planthopper (BPH) is one of the most destructive insects affecting rice (Oryza sativaL.) production. Phenylalanine ammonia-lyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority ofPALsin rice is significantly induced by BPH feeding. Knockdown of OsPALssignificantly reduces BPH resistance, whereas overexpression ofOsPAL8in a susceptible rice cultivar significantly enhances its BPH resistance. We found thatOsPALsmediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression ofOsPAL6andOsPAL8in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice.