Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
NATURE COMMUNICATIONS
Authors: Zaidi, Syed H.; Harrison, Tabitha A.; Phipps, Amanda, I; Steinfelder, Robert; Trinh, Quang M.; Qu, Conghui; Banbury, Barbara L.; Georgeson, Peter; Grasso, Catherine S.; Giannakis, Marios; Adams, Jeremy B.; Alwers, Elizabeth; Amitay, Efrat L.; Barfield, Richard T.; Berndt, Sonja, I; Borozan, Ivan; Brenner, Hermann; Brezina, Stefanie; Buchanan, Daniel D.; Cao, Yin; Chan, Andrew T.; Chang-Claude, Jenny; Connolly, Charles M.; Drew, David A.; Farris, Alton Brad, III; Figueiredo, Jane C.; French, Amy J.; Fuchs, Charles S.; Garraway, Levi A.; Gruber, Steve; Guinter, Mark A.; Hamilton, Stanley R.; Harlid, Sophia; Heisler, Lawrence E.; Hidaka, Akihisa; Hopper, John L.; Huang, Wen-Yi; Huyghe, Jeroen R.; Jenkins, Mark A.; Krzyzanowski, Paul M.; Lemire, Mathieu; Lin, Yi; Luo, Xuemei; Mardis, Elaine R.; McPherson, John D.; Miller, Jessica K.; Moreno, Victor; Mu, Xinmeng Jasmine; Nishihara, Reiko; Papadopoulos, Nickolas; Pasternack, Danielle; Quist, Michael J.; Rafikova, Adilya; Reid, Emma E. G.; Shinbrot, Eve; Shirts, Brian H.; Stein, Lincoln D.; Teney, Cherie D.; Timms, Lee; Um, Caroline Y.; Van Guelpen, Bethany; Van Tassel, Megan; Wang, Xiaolong; Wheeler, David A.; Yung, Christina K.; Hsu, Li; Ogino, Shuji; Gsur, Andrea; Newcomb, Polly A.; Gallinger, Steven; Hoffmeister, Michael; Campbell, Peter T.; Thibodeau, Stephen N.; Sun, Wei; Hudson, Thomas J.; Peters, Ulrike
Abstract
Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
Plasma vascular non-inflammatory molecule 3 is associated with gastrointestinal acute graft-versus-host disease in mice
JOURNAL OF INFLAMMATION-LONDON
Authors: Wang, Na; Qin, Xiaoyi; Cao, Yigeng; Liang, Bin; Yu, Kang; Ye, Haige
Abstract
Background: Gastrointestinal acute graft-versus-host disease (GI aGVHD) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT). However, it is still very difficult to make a diagnosis of GI aGVHD in practice. To date, no consensus plasma biomarker of GI aGVHD can be used to help make a diagnosis. Here, we attempted to identify GI aGVHD associated plasma proteins in murine model, which can help make a diagnosis of GI aGVHD. Methods: We used 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) to screen out proteins in plasma samples taken from murine models before and after allogeneic HSCT. Next mRNA expressions were validated by quantitative real-time polymerase chain reaction in mouse intestinal epithelial samples. Results: We found that five proteins were increased at least 2-fold in the allogeneic group at day 7 compared with days 0, 3 and 15 (after Cyclosporin A treatment) and the syngeneic group at day 7. These 5 proteins were VNN3, ZNF746, C4BP, KNG1 and FETUB, and they were consistent with results from negative labeling with 8-plex iTRAQ. Furthermore, increase in mRNA level of VNN3 was confirmed in murine intestinal epithelial samples with aGVHD. Conclusions: Our results demonstrate that plasma VNN3 protein is associated with GI aGVHD in murine model.
COA
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