Editorial Comment

Percutaneous Computerized Tomography Guided Cryoablation for Localized Renal Cell Carcinoma: Factors Influencing Success

American Journal of Medical Genetics Part AVolume 131A, Issue 1 p. 109-110 Correspondence In reply to: Proving pathogenicity—when evolution is not enough Fernando Scaglia, Corresponding Author Fernando Scaglia [email protected] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasAssistant Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030.Search for more papers by this authorHannes Vogel, Hannes Vogel Department of Pathology, Stanford University, Stanford, CaliforniaSearch for more papers by this authorEdith P. Hawkins, Edith P. Hawkins Department of Pathology, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorGeorgirene D. Vladutiu, Georgirene D. Vladutiu Department of Pediatrics, Division of Genetics, School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, New YorkSearch for more papers by this authorMin-Xin Guan, Min-Xin Guan Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioSearch for more papers by this authorLing-Ling Liu, Ling-Ling Liu Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this authorLee-Jun C. Wong, Lee-Jun C. Wong Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this author Fernando Scaglia, Corresponding Author Fernando Scaglia [email protected] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasAssistant Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030.Search for more papers by this authorHannes Vogel, Hannes Vogel Department of Pathology, Stanford University, Stanford, CaliforniaSearch for more papers by this authorEdith P. Hawkins, Edith P. Hawkins Department of Pathology, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorGeorgirene D. Vladutiu, Georgirene D. Vladutiu Department of Pediatrics, Division of Genetics, School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, New YorkSearch for more papers by this authorMin-Xin Guan, Min-Xin Guan Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioSearch for more papers by this authorLing-Ling Liu, Ling-Ling Liu Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this authorLee-Jun C. Wong, Lee-Jun C. Wong Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this author First published: 14 September 2004 https://doi.org/10.1002/ajmg.a.30319Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume131A, Issue115 November 2004Pages 109-110 RelatedInformation

Weight Loss Prevents Urinary Incontinence in Women With Type 2 Diabetes: Results From the Look AHEAD Trial

Alternative splicing variability: exactly how similar are two identical cells?

Impact of Anatomical and Socioeconomic Factors on Timing of Urological Consultation for Boys With Cryptorchidism

Successful Integration of Advanced Practice Providers Into a Pediatric Academic Community Intensive Care Unit

UPPER URINARY TRACT MANIFESTATIONS OF THE VACTERL ASSOCIATION

Reply by Authors.

A series of reports in 2007 established that single nucleotide polymorphisms (SNPs) in the 9p21.3 locus are associated with coronary heart disease (CHD), both in patients with acute myocardial infarction and chronic atherosclerosis.1,–,4 Subsequently, many additional studies used a candidate locus approach to replicate the 9p21.3-CHD association. Intriguingly, other phenotypes have also been found to be associated with this genomic region, including type II diabetes, stroke, malignant melanoma, aortic aneurysms, cerebral aneurysms, and periodontitis. Unfortunately, neither the causative variants nor genes have been established. Although genetic associations may permit better disease risk stratification, without the knowledge of the genes and variants we lose opportunities to improve our basic understanding of the disease process and hence the potential for targeted therapies. Article see p 445 Many cellular pathways in multiple tissues contribute to the pathogenic processes resulting in CHD. There is value in using intermediate phenotypes as outcomes in genetic association studies because there is enhanced power to detect gene associations when the number of genes potentially responsible for the phenotype is reduced, thereby increasing the fraction of the variance explained by any single factor or gene. In addition, intermediate traits are usually easier to define (have less heterogeneity) than clinical disease. Somewhat surprisingly, 9p21.3 has not been associated with measures believed to represent the chronic process of atherosclerosis or endothelial cell reactivity,5 suggesting that this locus may contribute to CHD by an alternate pathophysiologic mechanism. There is abundant pathological and clinical evidence demonstrating the vital role played by blood platelets in acute coronary syndromes, which result from the formation of occlusive platelet thrombi in coronary arteries at the sites of ruptured atherosclerotic plaques,6,7 and antiplatelet agents have become a mainstay of therapy in patients with acute coronary syndromes. In addition to …

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

Experience With 100 Cases Treated With Botulinum-A Toxin Injections in the Detrusor Muscle for Idiopathic Overactive Bladder Syndrome Refractory to Anticholinergics

Metastatic Carcinoid Tumor of the Prostate

Post-translational modification by covalent attachment of isoprenoid lipids (prenylation) regulates the functions and biological activities of several proteins implicated in the oncogenic transformation and metastatic progression of cancer. The largest group of prenylated proteins contains a CAAX motif at the C-terminal that serves as a substrate for a series of post-translational modifications that convert these otherwise hydrophilic proteins to lipidated proteins, thus facilitating membrane association. C17orf37 (chromosome 17 open reading frame 37), also known as C35/Rdx12/MGC14832, located in the 17q12 amplicon, is overexpressed in human cancer, and its expression correlates with the migratory and invasive phenotype of cancer cells. Here we show that C17orf37 contains a functional CAAX motif and is post-translationally modified by protein geranylgeranyltransferase-I (GGTase-I). Geranylgeranylation of C17orf37 at the CAAX motif facilitates association of the protein to the inner leaflet of plasma membrane, enhances migratory phenotype of cells by inducing increased filopodia formation, and potentiates directional migration. A prenylation-deficient mutant of C17orf37 is functionally inactive and fails to trigger dissemination of tail vein-injected cells in a mouse model of metastasis. These findings demonstrate that prenylation is required for the function of the C17orf37 protein in cancer cells and imply that the post-translational modification may functionally regulate metastatic progression of disease.

Sperm count and sperm motility in incidental high-grade varicocele

Semiautomated Multiplexed Quantum Dot-Based in Situ Hybridization and Spectral Deconvolution