NOTCH1 is recurrently mutated in chronic lymphocytic leukemia (CLL), most commonly as a two base-pair frameshift deletion (c.7541_7542delCT). This mutated allele encodes a truncated form of the receptor (P2514fs*4) lacking the C-terminal PEST degradation domain, and results in increased NOTCH1 signaling duration. NOTCH1 mutation has been associated with poor clinical outcomes in CLL. We sought to validate a highly sensitive and quantitative droplet digital PCR (ddPCR) assay for the NOTCH1 delCT mutation which we anticipated would perform well as compared to Sanger sequencing and allele-specific PCR. Performance characteristics of this assay were tested on 126 samples from an unselected CLL cohort, and a separate cohort of 85 samples from patients with trisomy 12 CLL. The delCT mutation was detected at allele frequencies as low as 0.024% and found 25% of unselected cases and 55% of trisomy 12 cases were positive at the 0.024% detection threshold. Mutational burdens ≥1% were found to be significantly associated with shorter overall survival (OS) in patients with trisomy 12+ disease in multivariate analysis (median OS 9.1 vs. 13 years with hazard ratio of 2.34; p=0.031). Mutational burdens <1% correlated with shorter OS in univariate, but not multivariate analyses. These results suggest ddPCR testing for NOTCH1 delCT mutation may prove useful for risk stratification and/or disease monitoring in certain subsets of patients with CLL.Copyright © 2020. Published by Elsevier Inc.
Open triple therapy for chronic obstructive pulmonary disease: Patterns of prescription, exacerbations and healthcare costs from a large Italian claims database.
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April 28, 2020
- ASCO – Lung CancerASCO.20 Virtual Scientific Program, held May 29 - 31, brought professionals from all over the world together to hear the brightest minds in oncology present state-of-the-art treatment modalities and new therapies.
- AACR-2020The American Association for Cancer Research is the world's oldest and largest professional association related to cancer research.
- ACC 2020The American College of Cardiology decided to cancel ACC.20/WCC due to COVID-19, which was scheduled to take place March 28-30 in Chicago. However, ACC.20/WCC Virtual Meeting continues to release cutting edge science and practice changing updates for cardiovascular professionals on demand and free through June 2020.
ASCO 2019The 2019 ASCO Annual Meeting, taking place May 31-June 4 in Chicago, will bring together more than 32,000 oncology professionals from across the globe. The theme of this year’s conference is Caring for Every Patient, Learning From Every Patient.