Open reading frame dominance indicates protein-coding potential of RNAs.

Recent studies have identified numerous RNAs with both coding and noncoding functions. However, the sequence characteristics that determine this bifunctionality remain largely unknown. In the present study, we develop and test the open reading frame (ORF) dominance score, which we define as the fraction of the longest ORF in the sum of all putative ORF lengths.

Accounting for EGFR Mutations in Epidemiologic Analyses of Non-Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data.

Background: Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches.

Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence.

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates.

Novel insights into immunohistochemical analysis for diagnosing serous neoplasm of the pancreas: aquaporin 1, stereocilin, and transmembrane protein 255B.

Aims: Serous (cystic) neoplasm (SCN) of the pancreas is generally benign, and surgical treatment is recommended in only a limited number of cases. To avoid unnecessary surgery, an accurate diagnosis of SCN is essential. In the present study, we aimed to identify new immunohistochemical markers with which to distinguish SCN from other tumours.

Hereditary diffuse gastric cancer: updated clinical practice guidelines.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome that is characterised by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is largely caused by inactivating germline mutations in the tumour suppressor gene CDH1, although pathogenic variants in CTNNA1 occur in a minority of families with HDGC. In this Policy Review, we present updated clinical practice guidelines for HDGC from the International Gastric Cancer Linkage Consortium (IGCLC), which recognise the emerging evidence of variability in gastric cancer risk between families with HDGC, the growing capability of endoscopic and histological surveillance in HDGC, and increased experience of managing long-term sequelae of total gastrectomy in young patients.

USP42 enhances homologous recombination repair by promoting R-loop resolution with a DNA-RNA helicase DHX9.

The nucleus of mammalian cells is compartmentalized by nuclear bodies such as nuclear speckles, however, involvement of nuclear bodies, especially nuclear speckles, in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, identified transcription-related nuclear speckle factors as potential HR regulators. Among the top hits, we provide evidence showing that USP42, which is a hitherto unidentified nuclear speckles protein, promotes HR by facilitating BRCA1 recruitment to DSB sites and DNA-end resection.

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis.

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals.

Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.

Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium.

Towards Circulating-Tumor DNA-Based Precision Medicine.

In the era of precision medicine, targeted therapies have been implemented for various diseases. Genomic information guides decision-making in cancer treatment. The improvements in next-generation sequencing and polymerase chain reaction have made it possible to access the genetic information using circulating-tumor DNAs (ctDNAs).

Feasibility of resecting the portal vein only when necessary during pancreatoduodenectomy for pancreatic cancer.

Background: Whether the portal/superior mesenteric vein (PV) should be resected during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) based on preoperative CT or intraoperative findings is controversial.

Methods: This was a retrospective study with data of patients who had undergone pancreatoduodenectomy for PDAC between 2002 and 2016 in a tertiary referral centre. Based on the extent of contact between the PV and tumour on CT, patients were categorized into: group 1, no contact; group 2, contact 180° or less; group 3, contact greater than 180°.

KMT2A (MLL) fusions in aggressive sarcomas in young adults.

Aim: To characterise unclassifiable sarcomas by use of a combined histological and molecular approach.

Methods And Results: Using RNA sequencing, we identified in-frame fusions involving KMT2A (MLL) in two cases. Case 1 was a 20-year-old woman with a deep soft tissue mass in the thigh.

Frequent false-negative immunohistochemical staining with IDH1 (R132H)-specific H09 antibody on frozen section control slides: a potential pitfall in glioma diagnosis.

Aims: Intraoperative consultation using frozen sections (FSs) is an integral component of clinical practice. As a quality control measure, FS diagnosis is subsequently compared with the findings on a FS control slide. These control slides can be used for immunohistochemistry, and the immunohistochemical performance in FS controls is known to be antibody-dependent.

Extent of lymph node dissection in patients with gallbladder cancer.

Background: Definitions of regional lymph nodes for gallbladder cancer differ according to staging system. Hence, the appropriate extent of lymph node dissection has not yet been standardized.

Methods: Pathological stages and disease-specific survival (DSS) of patients who had undergone surgical resection of gallbladder cancer between 1990 and 2016 were reviewed.

How to stomach an epigenetic insult: the gastric cancer epigenome.

Gastric cancer is a deadly malignancy afflicting close to a million people worldwide. Patient survival is poor and largely due to late diagnosis and suboptimal therapies. Disease heterogeneity is a substantial obstacle, underscoring the need for precision treatment strategies.

CIC break-apart fluorescence in-situ hybridization misses a subset of CIC-DUX4 sarcomas: a clinicopathological and molecular study.

Aims: Approximately 60-70% of high-grade round-cell sarcomas that lack the Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement harbour a rearrangement of the CIC gene, most commonly CIC-DUX4. Recent studies have established that CIC-rearranged sarcomas constitute a distinct group characterized by recognizable histology and immunoprofiles, such as positivity for ETV4 and WT1 and negativity for NKX2.2.

Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion.

Aims: Immunohistochemistry for mismatch repair (MMR) proteins is being increasingly used to examine MMR status in tumours. The aim of the present article was to report the case of a colon cancer patient with Lynch syndrome who showed unusual cytoplasmic MMR protein localization.

Methods And Results: Histologically, the colon cancer was diagnosed as medullary carcinoma associated with prominent tumour-infiltrating lymphocytes and a Crohn's-like reaction.

Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours.

Aims: The diagnosis of a malignant peripheral nerve sheath tumour (MPNST) can be challenging, as the morphological criteria and existing immunohistochemical markers are not entirely specific. The recent discovery of frequent inactivation of polycomb repressive complex 2 in MPNSTs suggests that immunohistochemical detection of histone 3 trimethylated on lysine 27 (H3K27me3) could be of diagnostic help. This study aimed to clarify the utility of this marker.

High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial.

Recent reports described the NUP98-NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98-NSD1 fusion. PRDM16 gene expression levels were measured via real-time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio ≥0·010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs.

Mucinous micropapillary pattern in lung adenocarcinomas: a unique histology with genetic correlates.

Aims: In lung adenocarcinoma (ADC), micropapillary carcinomas (MPCs) are associated with poor prognosis because these tumours exhibit higher metastatic potential. Despite this, there are no studies investigating the differences between mucinous and non-mucinous MPC.

Methods And Results: We evaluated the proportion of micropapillary components in lung ADCs, and compared the differences with respect to the presence or absence of associated mucin.

Biomarker expression and druggable gene alterations for development of an appropriate therapeutic protocol for pulmonary adenosquamous carcinoma.

Aims: Pulmonary adenosquamous carcinoma (ASC) is more aggressive than adenocarcinoma (AC) and squamous cell carcinoma (SCC). The genetic features and biomarkers of ASC are not well known. Here, we attempted to identify potential therapeutic markers for ASC.

Gene expression network analysis of ETV1 reveals KCTD10 as a novel prognostic biomarker in gastrointestinal stromal tumor.

Background: Prognostic biomarkers are required for risk stratification therapy in the patients with gastrointestinal stromal tumor (GIST). In this study, we aimed to identify prognostic biomarkers in GIST. We assessed the prognostic value of E twenty-six variant 1 (ETV1), a recently identified transcription factor unique to GIST.

Combined functional genome survey of therapeutic targets for clear cell carcinoma of the kidney.

Objective: Emerging molecular targeting therapeutics have been incorporated into the management of advanced renal cell carcinoma; however, their efficacy remains limited. The aim of this study was to catalog potential therapeutic target molecules for renal cell carcinoma.

Methods: We first selected genes up-regulated in clear cell renal cell carcinoma relative to surrounding normal kidney tissues in 10 patients (Study Cohort) using high-density exon arrays that detect all potential transcripts predicted in the human genome.

Overexpression of α-methylacyl-CoA racemase is associated with CTNNB1 mutations in hepatocellular carcinomas.

Aims: α-Methylacyl-CoA racemase (AMACR) is expressed in the majority of hepatocellular carcinomas (HCCs) at variable levels, but the significance of AMACR overexpression remains elusive. The aim of this study was to investigate the relationship between AMACR expression and the presence of CTNNB1 mutations in HCCs.

Methods And Results: The expression of AMACR and GLUL, an established downstream target of β-catenin was examined in HCCs, by quantitative reverse transcription polymerase chain reaction (PCR), and the expression of their protein products by immunohistochemistry.

Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma.

Pulmonary metastasis is the most significant prognostic determinant for osteosarcoma, but methods for its prediction and treatment have not been established. Using oligonucleotide microarrays, we compared the global gene expression of biopsy samples between seven osteosarcoma patients who developed pulmonary metastasis within 4 years after neoadjuvant chemotherapy and curative resection, and 12 patients who did not relapse. We identified argininosuccinate synthetase (ASS) as a gene differentially expressed with the highest statistical significance (Welch's t test, P = 2.