TP53 Exon 5 Mutation Indicates Poor Progression-Free Survival for Patients with Stage IV NSCLC.

BACKGROUND: Genetic mutations are quite common in non-small cell lung cancer (NSCLC), however, their prognostic value remains controversial. METHODS: This study explored the mutational landscape of tumor samples from patients with advanced NSCLC by next-generation sequencing (NGS). A total of 101 NSCLC patients in stage III or IV receiving first-line treatment were included. RESULTS: TP53 mutation was the most frequent genetic alteration in NSCLC tumors (68%), followed by EGFR (49%), CDKN2A (12%), LRP1B (9%), and FAT3 (9%) mutations. Among 85 patients with stage IV NSCLC, first-line targeted therapy remarkably prolonged progression-free survival (PFS) of patients compared with first-line chemotherapy (p = 0.0028). Among 65 patients with stage IV NSCLC whose tumors harbored EGFR, ALK, ROS, or BRAF mutations, first-line targeted therapy substantially prolonged the PFS of patients (p = 0.0027). In patients with TP53 mutations who received first-line targeted therapy or chemotherapy, missense mutation was the most common mutation type (36/78), and exon 5 represented the most common mutated site (16/78). CONCLUSIONS: TP53 mutation in exon 5 could independently predict poor PFS of patients with stage IV NSCLC after the first- line treatment. Moreover, mutations in TP53 exon 5 and LRP1B were associated with shorter PFS of such patients whether after first-line chemotherapy or targeted therapy, respectively. Thus, these patients should be given immunotherapy or immunochemotherapy.

Characterization of the primate TRIM gene family reveals the recent evolution in primates.

The tripartite motif (TRIM) gene family encodes diverse distinct proteins that play important roles in many biological processes. However, the molecular evolution and phylogenetic relationships of TRIM genes in primates are still elusive. We performed a genomic approach to identify and characterize TRIM genes in human and other six primate genomes. In total, 537 putative functional TRIM genes were identified and TRIM members varied among primates. A neighbor joining (NJ) tree based on the protein sequences of 82 human TRIM genes indicates seven TRIM groups, which is consistent with the results based on the architectural motifs. Many TRIM gene duplication events were identified, indicating a recent expansion of TRIM family in primate lineages. Interestingly, the chimpanzee genome shows the greatest TRIM gene expansion among the primates; however, its congeneric species, bonobo, has the least number of TRIM genes and no duplication event. Moreover, we identified a ~ 200 kb deletion on chromosome 11 of bonobos that results in a loss of cluster3 TRIM genes. The loss of TRIM genes might have occurred within the last 2 mys. Analysis of positive selection recovered 9 previously reported and 21 newly identified positively selected TRIM genes. In particular, most positive selected sites are located in the B30.2 domains. Our results have provided new insight into the evolution of primate TRIM genes and will broaden our understanding on the functions of the TRIM family.

Comparative genomic analysis and multi-drug resistance differences of Acinetobacter baumannii in Chongqing, China.

INTRODUCTION: Multidrug-resistance in Acinetobacter baumannii has emerged as a serious problem to public health. There is still a significant gap in the understanding of the multidrug-resistance and the genome diversity evolutionary process of A. baumannii in China, especially in the central and western regions. METHODS: Ten A. baumannii strains were collected from three hospitals in Chongqing, China. Whole-genome re-sequencing was used to obtain differences in genomic levels among strains. The diversity were determined by multi-locus sequence typing method, and investigate the genetic relationship between the ten strains and others by phylogenetic analysis. Comparative analysis focused on resistance genes related to insertions and deletions (InDels) and single-nucleotide polymorphisms (SNPs) was performed. RESULTS: The overall G+C% content was 39.05%~39.43%, the average sequencing depth was 273.95~428.99, and the alignment ratio of the sequencing data was 92.93%~99.27%. A total of 42 InDels and 11,387 SNPs were detected in the coding sequence region of the isolates. Phylogenetic tree shows that the 10 A. baumannii isolates were divided into four relative groups, and there exist the possibility of cross-regional spread pattern. A total number of 19 drug resistance genes had been found in each strain, and efflux pump-related genes accounted for the most. Only AacA4 underwent a change in InDel. Six types of drug resistance genes were found in the SNPs resistance gene-related loci, among which gene ANT(3'')-II and QacE mutations were found in each strain. CONCLUSION: In this study, the main mechanism of A. baumannii multi-drug resistance is due to the multi-drug efflux pump related genes. The point mutations at the SNPs sites of the six types of resistance genes are the main differences in A. baumannii between Chongqing and the eastern coastal areas of China.

The draft genome sequence of forest musk deer (Moschus berezovskii).

Background: The forest musk deer, Moschus berezovskii, is one of seven musk deer (Moschus spp.) and is distributed in Southwest China. Akin to other musk deer, the forest musk deer has been traditionally and is currently hunted for its musk (i.e., global perfume industry). Considerable hunting pressure and habitat loss have caused significant population declines. Consequently, the Chinese government commenced captive breeding programs for musk harvesting in the 1950s. However, the prevalence of fatal diseases is considerably restricting population increases. Disease severity and extent are exacerbated by inbreeding and genetic diversity declines in captive musk deer populations. It is essential that knowledge of captive and wild forest musk deer populations' immune system and genome be gained in order to improve their physical and genetic health. We have thus sequenced the whole genome of the forest musk deer, completed the genomic assembly and annotation, and performed preliminary bioinformatic analyses. Findings: A total of 407 Gb raw reads from whole-genome sequencing were generated using the Illumina HiSeq 4000 platform. The final genome assembly is around 2.72 Gb, with a contig N50 length of 22.6 kb and a scaffold N50 length of 2.85 Mb. We identified 24,352 genes and found that 42.05% of the genome is composed of repetitive elements. We also detected 1,236 olfactory receptor genes. The genome-wide phylogenetic tree indicated that the forest musk deer was within the order Artiodactyla, and it appeared as the sister clade of four members of Bovidae. In total, 576 genes were under positive selection in the forest musk deer lineage. Conclusions: We provide the first genome sequence and gene annotation for the forest musk deer. The availability of these resources will be very useful for the conservation and captive breeding of this endangered and economically important species and for reconstructing the evolutionary history of the order Artiodactyla.

Comparison of microsatellite distribution in genomes of Centruroides exilicauda and Mesobuthus martensii.

In this study, we characterized the distribution of microsatellites in the genomes and genes of Centruroides exilicauda and Mesobuthus martensii, carried out Gene Ontology (GO) analysis and GO enrichment analysis of coding sequences (CDSs) with microsatellite (SSR). In addition, over-represented GO functions related to environmental interactions, development process and methylation were identified to develop functional markers and facilitate further analysis of microsatellite function in the genes of scorpions. Location analysis indicated that microsatellites were predominantly concentrated at both ends of genes. Most genes containing microsatellite had the SSR present at only one locus, from which we infer that the number of SSRs per gene is limited even though intragenic tandem repeats can generate functional variability. Lastly, we identified 75 SSRs in 64 genes of 54 expanded gene families and 1 SSR in the toxin gene of Mesobuthus martensii, allowing future studies on the effect of microsatellites on gene function.

Profile of microRNA in Giant Panda Blood: A Resource for Immune-Related and Novel microRNAs.

The giant panda (Ailuropoda melanoleuca) is one of the world's most beloved endangered mammals. Although the draft genome of this species had been assembled, little was known about the composition of its microRNAs (miRNAs) or their functional profiles. Recent studies demonstrated that changes in the expression of miRNAs are associated with immunity. In this study, miRNAs were extracted from the blood of four healthy giant pandas and sequenced by Illumina next generation sequencing technology. As determined by miRNA screening, a total of 276 conserved miRNAs and 51 novel putative miRNAs candidates were detected. After differential expression analysis, we noticed that the expressions of 7 miRNAs were significantly up-regulated in young giant pandas compared with that of adults. Moreover, 2 miRNAs were up-regulated in female giant pandas and 1 in the male individuals. Target gene prediction suggested that the miRNAs of giant panda might be relevant to the expressions of 4,602 downstream genes. Subseuqently, the predicted target genes were conducted to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and we found that these genes were mainly involved in host immunity, including the Ras signaling pathway, the PI3K-Akt signaling pathway, and the MAPK signaling pathway. In conclusion, our results provide the first miRNA profiles of giant panda blood, and the predicted functional analyses may open an avenue for further study of giant panda immunity.

First insights into the giant panda (Ailuropoda melanoleuca) blood transcriptome: a resource for novel gene loci and immunogenetics.

The giant panda (Ailuropoda melanoleuca) is one of the most famous flagship species for conservation, and its draft genome has recently been assembled. However, the transcriptome is not yet available. In this study, the blood transcriptomes of three pandas were characterized and about 160 million sequencing reads were generated using Illumina HiSeq 2000 paired-end sequencing technology. The assembly yielded 92 598 transcripts with an average length of 1626 bp and N50 length of 2842 bp. Based on a sequence similarity search against nonredundant (nr) protein database, a total of 38 522 (41.6%) transcripts were annotated. Of these annotated transcripts, 25 142 and 8272 transcripts were assigned to gene ontology terms and clusters of orthologous group, respectively. A search against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG) indicated that 9098 (9.83%) transcripts mapped to 324 KEGG pathways, and the best represented functional categories of pathways were signal transduction and immune system. We have also identified 23 460 microsatellites, 43 560 SNPs as well as 21 456 alternative splicing events in the assembly. Additionally, a total of 24 341 complete open reading frames (ORFs) were detected from the assembly where 1492 ORFs were found to be novel gene loci as these have not been annotated so far in any public database.