Solution structure of all parallel G-quadruplex formed by the oncogene RET promoter sequence

RET protein functions as a receptor-type tyrosine kinase and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the promoter plays an important role in the transcriptional regulation of RET. Here, we report the NMR solution structure of the major intramolecular G-quadruplex formed on the G-rich strand of this region in K+ solution. The overall G-quadruplex is composed of three stacked G-tetrad and four syn guanines, which shows distinct features for all parallel-stranded folding topology. The core structure contains one G-tetrad with all syn guanines and two other with all anti-guanines. There are three double-chain reversal loops: the first and the third loops are made of 3 nt G-C-G segments, while the second one contains only 1 nt C10. These loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure and their conformations are in accord with the experimental mutations. The distinct RET promoter G-quadruplex structure suggests that it can be specifically involved in gene regulation and can be an attractive target for pathway-specific drug design

Case of reversible diabetes mellitus in the setting of benign pheochromocytoma

Pheochromocytomas have been shown to impair glucose tolerance and, rarely, to precipitate overt diabetes mellitus. We report here a case of a large pheochromocytoma in a woman with a recent diagnosis of diabetes mellitus that proved difficult to control despite high-dose insulin therapy who had complete resolution of her hyperglycemia following adrenalectomy. Her dramatic presentation demonstrates the need to consider this etiology in patients with new-onset insulin resistance and hypertension. Keywords: Pheochromocytoma, Insulin resistance, Impaired glucose tolerance, Diabetes mellitu

Non-epithelial Renal Neoplasms of the Adult Kidney

Non-epithelial renal neoplasms are usually incidentally discovered and generally appear as solid enhancing lesions on computerized tomography. Mesenchymal lesions include angiomyolipoma, leiomyoma, hemangioma, solitary fibrous tumor, leiomyosarcoma, synovial sarcoma, and liposarcoma, with appearances and behaviors similar to those arising outside the kidney. Angiomyolipomas are the most common of these entities and classically contain varying amounts of adipose tissue, smooth muscle, and vessels. In contrast to classic angiomyolipoma, epithelioid angiomyolipoma can be associated with a malignant outcome. Other renal-specific mesenchymal renal neoplasms include juxtaglomerular cell tumor and renomedullary interstitial cell tumor, both of which represent benign entities. The primary therapy for most mesenchymal renal neoplasms is surgical excision with concomitant partial or complete resection of adjacent uninvolved structures when locally invasive. Embolization is another option, with chemotherapy and radiation mostly reserved for palliative purposes. In addition to mesenchymal lesions, the kidney may be involved rarely by primary renal lymphoma and have secondary involvement by lymphoma and leukemia. Finally, neuroendocrine lesions may also occur and represent a spectrum of entities ranging from renal carcinoid tumor to small cell carcinoma

Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations.

Cystic nephromas (CNs) are uncommon benign renal neoplasms that present with a bimodal age distribution, affecting either infants/young children or adult females. Although differences between these age groups have been suggested, large studies of pediatric CN have not been conducted. As a result, the nomenclature and diagnostic criteria for these lesions remains controversial. In addition, the morphological overlap seen between CN and cystic partially differentiated nephroblastoma (CPDN) can result in diagnostic dilemmas. This study reviews the morphologic and radiographic features of 44 pediatric CN prospectively enrolled on a Children's Oncology Group (COG) protocol from 2007 to 2013. While the typical multicystic architecture with thin septa described in adult CN was present in all of our pediatric cases, differences were also identified. We report distinctive features that add to the morphological spectrum of CN in children. Of the 44 cases, 16 had been previously analyzed and reported for DICER1 mutation, and either loss of function or missense mutations, or both, were identified in 15/16. In contrast, we analyzed 10 cases of adult CN and all were negative for DICER1 mutations; similarly 6 CPDNs previously analyzed and reported were negative for DICER1 mutations. Therefore, the clinical, morphological and genetic differences between pediatric and adult CN, as well as between CN and CPDN, suggest that these three lesions represent distinct entities

Clonal immunoglobulin DNA in the plasma of patients with AIDS lymphoma

Immunoglobulin (Ig) gene rearrangements are used to define clonality of suspected B-lineage malignancy in tissue samples. To determine whether such rearrangements could be identified in plasma, we screened plasma from 14 consecutive patients with AIDS-related lymphoma with multiplex Ig primers. Clonally rearranged Ig DNA was detected in plasma from 7 of 14 patients. Patients in whom clonal Ig DNA remained detectable after combination chemotherapy died with lymphoma. Tumor was available from 1 patient, and the IgH amplification products from plasma and tumor were sequenced and confirmed to be identical. Ig DNA rearrangements in plasma may be useful as a lymphoma-specific tumor marker, and failure to clear clonal Ig DNA may identify patients at high risk for failure of standard therapy