Public Release:  JCI early table of contents for June 17, 2013

Journal of Clinical Investigation

Scouring the genome of adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC) is a slow-growing and often fatal malignancy that can occur at multiple organ site, but is most frequently found in the salivary glands. The primary treatment is surgical removal; however, the majority of patients develop metastatic disease. In this issue of the Journal of Clinical Investigation, researchers led by Andrew Futreal at the Wellcome Trust Sanger Institute in Cambridge, MA, performed a type of genetic sequencing known as whole exome sequencing of 24 ACC cases. They identified a genetic translocation that can precipitate disease and determined that a large number of disease-associated mutations occurred in genes that modify DNA. In the accompanying commentary, Henry Frierson, Jr. of the University of Virginia emphasizes that identifying individual mutations will aid the development of personalized therapy.

TITLE: Whole exome sequencing of adenoid cystic carcinoma

AUTHOR CONTACT: P. Andrew Futreal
Wellcome Trust Sanger Institute, Cambridge, GBR
Phone: 7137944764; E-mail:

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TITLE: Mutation signature of adenoid cystic carcinoma: evidence for transcriptional and epigenetic reprogramming

AUTHOR CONTACT: Henry Frierson
University of Virginia, Charlottesville, VA, USA
Phone: (434) 924-9171; E-mail:

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Variants in the SIM1 gene are associated with severe obesity

Although body weight is largely determined by lifestyle factors, increasingly research is revealing that genetics also play an important role in determining an individual's susceptibility to obesity. Identifying the mutations that underlie the fraction of obese patients with monogenic obesity can help us to understand complex processes like metabolic rate, eating behavior, growth, and fat storage. In this issue of the Journal of Clinical Investigation, two groups identified obesity-linked mutations in the gene SIM1. Sadaf Farooqi and colleagues at Addenbrooke's Hospital in Cambridge, England, identified thirteen SIM1 mutations in obese patients, and found that reduced SIM1 function correlated with increased food intake and altered nervous system dysfunction. In an independent study, Philippe Froguel and colleagues at Imperial College London identified eight SIM1 mutations in morbidly obese adults and in patients with a disorder resembling Prader-Willi syndrome. In the patients studied, loss of SIM1 function was associated with inherited obesity. Taken together, these studies confirm a strong link between SIM1 dysfunction and obesity.

TITLE: Rare variants in single-minded 1 (SIM1) are associated with severe obesity

Addenbrooke's Hospital, Cambridge, GBR
Phone: 44-1223-762-634; Fax: 44-1223-762-657; E-mail:

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TITLE: Loss-of-function mutations in SIM1 contribute to obesity and Prader-Willi-like features

AUTHOR CONTACT: Philippe Froguel
Imperial College London, London, GBR
Phone: +44 (0)20 8383 3989; Fax: +33-320.87.7229; E-mail:

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Vitamin B3 blocks cyst formation in a mouse model of polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder caused by mutations in PKD1 or PKD2 that predominately affects the kidneys and is characterized by the formation of cysts in the kidneys and other organs. Xiaogang Li and colleagues at the University of Kansas Medical Centr used a mouse model of ADPKD to explore the role of the protein sirtuin 1 in cyst formation. They found that inhibition of sirtuin 1 activity using vitamin B3 can reduced cyst formation in the kidneys of ADPKD mice. These findings suggest that therapeutics targeting sirtuin 1 could potentially be used to treat ADPKD.

TITLE: Sirtuin 1 inhibition delays cyst formation in autosomal dominant polycystic kidney disease

University of Kansas Medical Center, Kansas City, KS, USA
Phone: 913-588-2731; E-mail:

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TITLE: Dependence receptor UNC5D mediates nerve growth factor depletion-induced neuroblastoma regression

AUTHOR CONTACT: Akira Nakagawara
Chiba Cancer Center Research Institute, Chiba, UNK, JPN
Phone: 81-43-264-5431; Fax: 81-43-263-8175; E-mail:

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TITLE: Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Phone: 919-966-5471; E-mail:

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TITLE: CD4+ follicular helper T cell infiltration predicts breast cancer survival

AUTHOR CONTACT: Karen Willard-Gallo
Institut Jules Bordet, Brussels, UNK, BEL
Phone: +32-2-541-3739; Fax: +32-2-541-7325; E-mail:

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TITLE: iPSC derived beta cells model diabetes due to glucokinase deficiency

The New York Stem Cell Foundation, New York, NY, USA
Phone: 212-851-5422; E-mail:
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TITLE: Dysregulation of voltage-gated sodium channels by ubiquitin-ligase NEDD4-2 in neuropathic pain

Hugues Abriel University of Bern, Bern, CHE
Phone: +41316320998; E-mail:

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TITLE: CpG-depleted adeno-associated virus vectors evade immune detection

University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Phone: 215-898-0226; Fax: 215-494-5444; E-mail:

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