Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer.

BACKGROUND: The research emphasis in anti-cancer drug discovery has always been to search for a drug with the greatest antitumor potential but fewest side effects. This can only be achieved if the drug used is against a specific target located in the tumor cells. In this study, we evaluated Minichromosome Maintenance Protein 7 (MCM7) as a novel therapeutic target in cancer. RESULTS: Immunohistochemical analysis showed that MCM7 was positively stained in 196 of 331 non-small cell lung cancer (NSCLC), 21 of 29 bladder tumor and 25 of 70 liver tumor cases whereas no significant staining was observed in various normal tissues. We also found an elevated expression of MCM7 to be associated with poor prognosis for patients with NSCLC (P = 0.0055). qRT-PCR revealed a higher expression of MCM7 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpressed MCM7 by cDNA microarray analysis. Suppression of MCM7 using specific siRNAs inhibited incorporation of BrdU in lung and bladder cancer cells overexpressing MCM7, and suppressed the growth of those cells more efficiently than that of normal cell strains expressing lower levels of MCM7. CONCLUSIONS: Since MCM7 expression was generally low in a number of normal tissues we examined, MCM7 has the characteristics of an ideal candidate for molecular targeted cancer therapy in various tumors and also as a good prognostic biomarker for NSCLC patients.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Factors related to the number of missing teeth from a physiological, blood biochemical, and nutritional point of view

The aim of this study was to clarify the risk factors for tooth loss from a physiological, blood biochemical, and nutritional point of view. The subjects of this study were 364 people (224 males, 140 females). They were examinees of a medical examination center in Matsumoto Dental University Hospital. Using the number of teeth present (including sound, decayed, and filled teeth) as the response variable, a multiple regression analysis was conducted using parameters in the mouth, physiological parameters, blood biochemical parameters, and nutritional parameters as covariates. In the multiple regression analysis with the response variable as the number of teeth present, the significant influence of attachment loss, sugar–sweetener intake, age, and sodium intake was noted on a decreasing number of teeth in the study subjects. Thus, the number of teeth present was influenced by the physiological, blood biochemical, and nutritional condition. In the future, increasing the number of cases will be necessary along with long–term follow–up

Comprehensive analysis including the nutritional point of view on the pathogenesis of periodontal disease

To clarify risk factors for periodontal disease from the viewpoints of physiology, blood biochemistry, and nutrition, a survey involving 364 persons (224 males, 140 females) who consulted the Medical Examination Center of Matsumoto Dental University Hospital was conducted. The pathogenesis of periodontal disease was investigated using the maximum Community Periodontal Index (CPI) and Attachment Loss (AL) values, and their distributions with respect to the sex were analyzed using Wilcoxonʼs rank sum test. Based on the CPI and AL values, the subjects were divided into 3 groups: healthy (0), mild (1–2), and severe (3–4). The mean values obtained from the physiological, dental, blood biochemical, and nutritional findings in the 3 groups were analyzed using the multiple comparison test. Furthermore, their distributions with respect to sex and smoking in the 3 groups were analyzed using Fisherʼs direct probability test. A p–value of 0.05 was regarded as significant. Factors influencing the CPI included the sex (male), body mass index (BMI), abdominal circumference, diastolic blood pressure, AL, alanine aminotransferase (ALT), fasting blood glucose, neutral fat, HDL cholesterol, and smoking. Factors influencing the AL included the sex (male), age, current number of teeth, CPI, lipid intake, manganese intake, vitamin C intake, monounsaturated fatty acid intake, polyunsaturated fatty acid intake, n–6 fatty acid intake, fruit intake, and smoking. The results suggest that the physiological, blood biochemical, and nutritional states are involved in the pathogenesis of periodontal disease. The CPI was associated with metabolic error in the presence of metabolic syndrome. There was an association between the AL and diet as an environmental factor

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations

Background & Aims Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. Methods We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. Results We identified 32 significantly and commonly mutated genes including TP53 , KRAS , SMAD4 , NF1 , ARID1A , PBRM1 , and ATR , some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1 , BRCA2 , RAD51D , MLH1 , or MSH2 were detected in 11% (16/146) of BTC patients. Conclusions BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. Lay summary We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1 . Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts