ACTG2-Associated Visceral Myopathy With Chronic Intestinal Pseudoobstruction, Intestinal Malrotation, Hypertrophic Pyloric Stenosis, Choledochal Cyst, and a Novel Missense Mutation
INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
Authors: Collins, Rebecca R. J.; Barth, Bradley; Megison, Stephen; Pfeifer, Cory M.; Rice, Luke M.; Harris, Samar; Timmons, Charles F.; Rakheja, Dinesh
Abstract
Primary visceral myopathy caused by a pathogenic mutation in the gene encoding the enteric smooth muscle actin gamma 2 (ACTG2) affects gastrointestinal and genitourinary tracts and often presents as chronic intestinal pseudoobstruction. We present a case of pediatric onset chronic intestinal pseudoobstruction associated with a novel missense ACTG2 mutation c.439G>T/p.G147C. In addition to the known disease manifestations of feeding intolerance and intestinal malrotation, our patient had a late-onset hypertrophic pyloric stenosis and a late-onset choledochal cyst, the former of which has not previously been described in patients with ACTG2-associated visceral myopathy.
Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling
ONCOGENE
Authors: Beck, A. H.; Lee, C-H; Witten, D. M.; Gleason, B. C.; Edris, B.; Espinosa, I.; Zhu, S.; Li, R.; Montgomery, K. D.; Marinelli, R. J.; Tibshirani, R.; Hastie, T.; Jablons, D. M.; Rubin, B. P.; Fletcher, C. D.; West, R. B.; van de Rijn, M.
Abstract
Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We used integrative molecular pro. ling to discover and characterize molecular subtypes of LMS. Gene expression pro. ling was performed on 51 LMS samples. Unsupervised clustering showed three reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and showed that the molecular subtypes defined by gene expression showed distinct genomic changes. Tumors from the 'muscle-enriched' cluster showed significantly increased copy number changes (P = 0.04). A majority of the muscle-enriched cases showed loss at 16q24, which contains Fanconi anemia, complementation group A, known to have an important role in DNA repair, and loss at 1p36, which contains PRDM16, of which loss promotes muscle differentiation. Immunohistochemistry (IHC) was performed on LMS tissue microarrays (n = 377) for five markers with high levels of messenger RNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP, CFL2 and MYLK) and showed significantly correlated expression of the five proteins (all pairwise P<0.005). Expression of the five markers was associated with improved disease-specific survival in a multivariate Cox regression analysis (P<0.04). In this analysis that combined gene expression pro. ling, aCGH and IHC, we characterized distinct molecular LMS subtypes, provided insight into their pathogenesis, and identified prognostic biomarkers. Oncogene (2010) 29, 845-854; doi:10.1038/onc.2009.381; published online 9 November 2009
COA
Certificate of Analysis
