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We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole‐exome sequencing (WES) was performed using DNA extracted from formalin‐fixed, paraffin‐embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression‐free survival (PFS) using a Cox regression model. We controlled for family‐wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57‐67 years), and 78.0% of the patients ultimately underwent surgery. The 3‐year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P =.00252 (Bonferroni‐adjusted significance level is.0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P <.05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC. [ABSTRACT FROM AUTHOR]

Common wheat (Triticum aestivum L.) is one of the most important cereals in the world. To improve wheat quality and productivity, the genomic sequence of wheat must be determined. The large genome size (∼17 Gb/1 C) and the hexaploid status of wheat have hampered the genome sequencing of wheat. However, flow sorting of individual chromosomes has allowed us to purify and separately shotgun-sequence a pair of telocentric chromosomes. Here, we describe a result from the survey sequencing of wheat chromosome 6B (914 Mb/1 C) using massively parallel 454 pyrosequencing. From the 4.94 and 5.51 Gb shotgun sequence data from the two chromosome arms of 6BS and 6BL, 235 and 273 Mb sequences were assembled to cover ∼55.6 and 54.9% of the total genomic regions, respectively. Repetitive sequences composed 77 and 86% of the assembled sequences on 6BS and 6BL, respectively. Within the assembled sequences, we predicted a total of 4798 non-repetitive gene loci with the evidence of expression from the wheat transcriptome data. The numbers and chromosomal distribution patterns of the genes for tRNAs and microRNAs in wheat 6B were investigated, and the results suggested a significant involvement of DNA transposon diffusion in the evolution of these non-protein-coding RNA genes. A comparative analysis of the genomic sequences of wheat 6B and monocot plants clearly indicated the evolutionary conservation of gene contents. [ABSTRACT FROM PUBLISHER]

Epigenetic alterations critically affect tumor development. Polycomb‐group complexes constitute an evolutionarily conserved epigenetic machinery that regulates stem cell fate and development. They are implicated in tumorigenesis, primarily via histone modification. Polycomb repressive complex 1 (PRC1) complexes 1–6 (PRC1.1–6) mediate the ubiquitination of histone H2A on lysine 119 (H2AK119ub). Here, we studied the functional roles of a PRC1.6 molecule, L3MBTL2, in neuroblastoma (NB) cells. L3MBTL2‐knockout and knockdown revealed that L3MBTL2 depletion suppressed NB cell proliferation via cell‐cycle arrest and gamma‐H2A.X upregulation. L3MBTL2‐knockout profoundly suppressed xenograft tumor formation. Transcriptome analysis revealed suppressed cell‐cycle‐related and activated differentiation‐related pathways. Break repair meiotic recombinase recruitment factor 1 (BRME1) and nuclear receptor interacting protein 3 (NRIP3) were notably de‐repressed by L3MBTL2‐knockout. The deletion of L3MBTL2 reduced enrichment of H2AK119ub and PCGF6 at transcriptional start site proximal regions of the targets. Add‐back studies unveiled the importance of L3MBTL2‐BRME1 and ‐NRIP3 axes for NB cell proliferation. We further manifested the association of MYCN with de‐repression of NRIP3 in an L3MBTL2‐deficient context. Therefore, this study first revealed the significance of L3MBTL2‐mediated gene silencing in MYCN‐amplified NB cells. [ABSTRACT FROM AUTHOR]

Phenotype prediction from genotype data is one of the most important issues in computational genetics. In this work, we propose a new kernel (i.e., an SVM: Support Vector Machine) method for phenotype prediction from genotype data. In our method, we first infer multiple suboptimal haplotype candidates from each genotype by using the HMM (Hidden Markov Model), and the kernel matrix is computed based on the predicted haplotype candidates and their emission probabilities from the HMM. We validated the performance of our method through experiments on several datasets: One is an artificially constructed dataset via a program GeneArtisan, others are a real dataset of the NAT2 gene from the international HapMap project, and a real dataset of genotypes of diseased individuals. The experiments show that our method is superior to ordinary naive kernel methods (i.e., not based on haplotype prediction), especially in cases of strong LD (linkage disequilibrium).