Exposure to per- and polyfluorinated alkyl substances in pregnant Brazilian women and its association with fetal growth
ENVIRONMENTAL RESEARCH
Authors: Oliveira Souza, Marilia Cristina; Saraiva, Maria Conceicao Pereira; Honda, Masato; Barbieri, Marco Antonio; Bettiol, Heloisa; Barbosa, Fernando; Kannan, Kurunthachalam
Abstract
Research pertaining to exposure of humans to per- and polyfluorinated alkyl substances (PFASs) has received considerable public and regulatory attention in recent years. Although several studies have reported exposure to PFASs by populations in North America and western Europe, such information is still scarce in Latin America, including Brazil. In this study, concentrations of thirteen PFASs were determined in whole blood collected during the second trimester from 252 pregnant Brazilian women. This is a nested case-control study within the Brazilian Ribeirao Preto and Sao Luiz Birth Cohort Study (BRISA) with selected birth outcomes cases (n = 63) and matched controls (n = 189). PFASs concentrations were associated with conditions including preeclampsia, birth weight (BW), preterm birth, and intrauterine growth restriction (IUGR). Among PFASs measured, per- fluorooctane sulfonate (PFOS) was found at the highest concentration (range: 1.06-106 ng(-1) with a median value of 3.41 ng mL(-1)) which was followed by perfluorooctanoic acid (PFOA, range: 0.11-2.77 ng mL(-1) with a median value of 0.20 ng mL(-1)). A significant positive association of PFOS and PFOA concentrations with fetal growth restriction (p < 0.05) was found. This is the first study to assess whole blood concentrations of PFASs and their effect on fetal growth in pregnant Brazilian women.
Dysregulation of cancer genes by recurrent intergenic fusions
GENOME BIOLOGY
Authors: Yun, Jae Won; Yang, Lixing; Park, Hye-Young; Lee, Chang-Woo; Cha, Hongui; Shin, Hyun-Tae; Noh, Ka-Won; Choi, Yoon-La; Park, Woong-Yang; Park, Peter J.
Abstract
Background Gene fusions have been studied extensively, as frequent drivers of tumorigenesis as well as potential therapeutic targets. In many well-known cases, breakpoints occur at two intragenic positions, leading to in-frame gene-gene fusions that generate chimeric mRNAs. However, fusions often occur with intergenic breakpoints, and the role of such fusions has not been carefully examined. Results We analyze whole-genome sequencing data from 268 patients to catalog gene-intergenic and intergenic-intergenic fusions and characterize their impact. First, we discover that, in contrast to the common assumption, chimeric oncogenic transcripts-such as those involvingETV4,ERG,RSPO3, andPIK3CA-can be generated by gene-intergenic fusions through splicing of the intervening region. Second, we find that over-expression of an upstream or downstream gene by a fusion-mediated repositioning of a regulatory sequence is much more common than previously suspected, with enhancers sometimes located megabases away. We detect a number of recurrent fusions, such as those involvingANO3,RGS9,FUT5,CHI3L1,OR1D4, andLIPGin breast;IGF2in colon;ETV1in prostate; andIGF2BP3andSIX2in thyroid cancers. Conclusion Our findings elucidate the potential oncogenic function of intergenic fusions and highlight the wide-ranging consequences of structural rearrangements in cancer genomes.