TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association with increased patient age. The prognostic implications of these mutations were highly subgroup-specific. TERT mutations identified a subset with good and poor prognosis in SHH and Group 4 tumors, respectively. Monosomy 6 was mostly restricted to WNT tumors without TERT mutations. Hallmark SHH focal copy number aberrations and chromosome 10q deletion were mutually exclusive with TERT mutations within SHH tumors. TERT promoter mutations are the most common recurrent somatic point mutation in medulloblastoma, and are very highly enriched in adult SHH and WNT tumors. TERT mutations define a subset of SHH medulloblastoma with distinct demographics, cytogenetics, and outcomes

A consensus document on bowel preparation before colonoscopy: Prepared by a Task Force from the American Society of Colon and Rectal Surgeons (ASCRS), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society of American Gastrointestinal

Colonoscopy is the most commonly used technique for inspection of the colonic mucosa. The safety and effectiveness of colonoscopy in identifying important colonic pathology is directly impacted by the quality of the bowel preparation performed in anticipation of the procedure. Physicians favor preparations associated with the best patient compliance to achieve the best results. Patients favor preparations that are low in volume, palatable, have easy to complete regimens, and are reimbursed by health insurance or are inexpensive. Both patients and physicians favor preparations that are safe to administer in light of existing comorbid conditions and those that will not interact with previously prescribed medications. Aqueous NaP solutions, NaP tablets, and PEG solutions, especially low-volume solutions, are all accepted and well tolerated by the majority of patients undergoing bowel preparation for colonoscopy. Physicians are advised to select a preparation for each patient based on the safety profile of the agent, NaP or PEG, in light of the overall health of the patient, their comorbid conditions, and currently prescribed medications. In certain circumstances, such as bowel preparation in children and some elderly patients, patients with renal insufficiency, and those with hypertension who are receiving ACE inhibitors or ARBs, it may be advisable to adhere to PEG-based solutions because of the risks of occult physiologic disturbances that may potentially contraindicate the use of NaP-based regimens. A variety of other preparations, none of which seem as popular because of inferior efficacy and/or patient acceptance, remain available for use in other circumstances in which bowel preparation is necessary. Many adjuncts to bowel preparation have been proposed but remain largely inefficacious and therefore cannot be recommended for routine use