A rare variant in EZH2 is associated with prostate cancer risk

Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5). Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild-type cases. Although no allele-dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers

Using primary sources to produce a microhistory of translation and translators: theoretical and methodological concerns

In descriptive studies, where the source and target texts are the main primary sources (‘primary text products’), ‘extra-textual’ sources are looked at with ‘circumspection’. However, in historical research methodologies they are central. This article examines the use and value of archives, manuscripts and, especially, translator papers, post-hoc accounts and interviews in producing a history of translation and translators. Rather than informing a ‘traditional’ Rankean history of facts and major personalities, the article underlines the potential value of such material in creating a ‘microhistory’, reclaiming the details of the everyday lives and working processes of sometimes little-known or forgotten translators and contextualising them to construct a social and cultural history of translation and translators. Sometimes these sources are housed in collections where translation may not be very visible, which creates problems of location. Examples are given from the autobiography of A. Birse and research on the working papers of Sam Hileman, Andrew Hurley, Bernard Miall and Margaret Sayers Peden

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers

Massively parallel sequencing in hereditary prostate cancer families reveals a rare risk variant in the DNA repair gene, RAD51C

[Extract] Dear Editor, Global statistics show that prostate cancer (PrCa) is the second most common non-cutaneous cancer diagnosed in men, and currently, it is the most commonly diagnosed cancer in Australian men [1]. While PrCa is a clinically complex, heterogeneous disease, it is one of the most heritable common cancers, with family history a strong predictor of susceptibility [2]. However, the identification of rare, high-risk germline variants for PrCa has lagged significantly behind other heritable cancers [3]

New Survey of London Life and Labour, 1929-1931

Abstract copyright UK Data Service and data collection copyright owner.The main aims of the research project were to computerise all the surviving records of the New Survey of London Life and Labour (1929-31), and to begin economic analysis of the data obtained. The specific objectives were: 1. To input the data in a manner which would preserve virtually all the information presented on the cards, and to ensure that the machine readable records replicate that information as faithfully as possible. 2. To organise the data in the form of a relational database 3. To check the data against the original cards, to code some of the variables (e.g. labour market status), and to correct inconsistencies in the original records. 4. To undertake separate coding sub-projects for occupations, birthplaces and street quality. 5. To document the results obtained in the form of a codebook and a companion paper to explain the methods employed in the computerisation. An earlier project was carried out in the USA in 1983-1986, based on the same data, involved computerisation of a 10% sample of the original source, plus a 50% sample of the households containing at least one unemployed person. That study is available from ICPSR - see New Survey of London Life and Labor, 1929-1931. Apart from the fact that they are both based on the same data source, there is no other connection between the two projects. Main Topics:The New Survey of London Life and Labour (NSLLL) survey was undertaken at the London School of Economics in 1929-31 to measure changes in living standards and in the scale and incidence of poverty among London's working class. It constitutes a unique source of microdata for economic and social history. One aim of the survey was to evaluate changes in working class living conditions since Charles Booth's pioneering survey of forty years earlier. The main component of the survey was a detailed household enquiry conducted mainly in the years 1929-31, during which information was collected on 28,000 households, about one in fifty of all working class households, in 38 London Boroughs. The pre-printed household record cards survive for 36 of the 38 boroughs and are held in the British Library of Economic and Political Science. The NSLLL is one of a number of social surveys, all essentially following the design established by Rowntree, Bowley and others. It was by far the greatest of these and the only one covering Britain's capital city. The NSLLL appears to be the only one of the social surveys conducted between 1900 and 1950 for which a significant number of the original record cards survive. It is therefore an unrivalled source for the analysis of economic and social conditions using modern computer methods. The cards include data on the demographic structure of each household, and household income and the earnings and work expenses of each earner in the household. In addition there is detailed information on housing conditions, the number and type of rooms occupied as well as type of tenure and rent paid and received. The information in the survey offers great potential for micro-socioeconomic research in a number of fields including poverty and welfare, labour markets and unemployment, migration and labour mobility, household structure and dependency, and the housing market. In March 1999, a second edition of this dataset was added to the Archive's collection. The new edition included some additional material : a file of workplace geographical location codes and adjacency codes providing information about the geographical relationship between each earner's borough of residence and borough of employment; a file of dates providing estimates of the year of interview (where this was possible and not already included on the interview card); amendments to the employment status code to signal those individuals for whom earnings were combined jointly with at least one other person in the same household (affects 191 earners); amendments to data for hours and earnings (the corrections affect approximately 40 individuals in about 30 households). Please note: this study does not include information on named individuals and would therefore not be useful for personal family history research. <br