Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia

Key Points LAPTM5 c403t and HCLS1g496a are potentially novel contributors for the genetic predisposition to familial WM. LAPTM5 c403t and HCLS1g496a represent possible candidates for screening in familial WM

Making Sense of Texts: a Meta-Analysis of College Students and Adults' Reading Strategies in a Hypermedia Environment

With the information influx from the hypermedia environment, queries have been made on the reading landscape, markedly related to college and adult readers, as they are perceived to have limited experience with the hypermedia environment. This environment calls on new literacies for a reader to cope with reading tasks inherent to its features. In this context, new challenges have been posed regarding online reading strategies of college and adult readers. With the dearth of literature about how college and adult readers navigate their way in their reading tasks in the hypermedia environment, this paper described their strategies in reading. The information gathered from the studies conducted before can contribute to the present plight of our readers who need to navigate their way through reading in a hypermedia environment. Eight studies that met the criteria on the variables of the study were included. The studies revealed the following reading strategies of college and adult readers: global, problem-solving, local, cognitive and metacognitive, and navigation strategies. This evidenced that print-based reading strategies are basics on which reading strategies in the hypermedia environment are built for strategic readers to be successful in their online reading tasks

Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution

Patients with chromosome 13q deletion or normal cytogenetics represent the majority of chronic lymphocytic leukaemia (CLL) cases, yet have relatively few driver mutations. To better understand their genomic landscape, here we perform whole-genome sequencing on a cohort of patients enriched with these cytogenetic characteristics. Mutations in known CLL drivers are seen in only 33% of this cohort, and associated with normal cytogenetics and unmutated IGHV. The most commonly mutated gene in our cohort, IGLL5, shows a mutational pattern suggestive of activation-induced cytidine deaminase (AID) activity. Unsupervised analysis of mutational signatures demonstrates the activities of canonical AID (c-AID), leading to clustered mutations near active transcriptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutations, and an ageing signature responsible for most mutations. Using mutation clonality to infer time of onset, we find that while ageing and c-AID activities are ongoing, nc-AID-associated mutations likely occur earlier in tumour evolution

Survival of Del17p CLL Depends on Genomic Complexity and Somatic Mutation.

PURPOSE: Chronic lymphocytic leukemia (CLL) with 17p deletion typically progresses quickly and is refractory to most conventional therapies. However, some del(17p) patients do not progress for years, suggesting that del(17p) is not the only driving event in CLL progression. We hypothesize that other concomitant genetic abnormalities underlie the clinical heterogeneity of del(17p) CLL. EXPERIMENTAL DESIGN: We profiled the somatic mutations and copy number alterations (CNA) in a large group of del(17p) CLLs as well as wild-type CLL and analyzed the genetic basis of their clinical heterogeneity. RESULTS: We found that increased somatic mutation number associates with poor overall survival independent of 17p deletion (P = 0.003). TP53 mutation was present in 81% of del(17p) CLL, mostly clonal (82%), and clonal mutations with del(17p) exhibit shorter overall survival than subclonal mutations with del(17p) (P = 0.019). Del(17p) CLL has a unique driver mutation profile, including NOTCH1 (15%), RPS15 (12%), DDX3X (8%), and GPS2 (6%). We found that about half of del(17p) CLL cases have recurrent deletions at 3p, 4p, or 9p and that any of these deletions significantly predicts shorter overall survival. In addition, the number of CNAs, but not somatic mutations, predicts shorter time to treatment among patients untreated at sampling. Indolent del(17p) CLLs were characterized by absent or subclonal TP53 mutation and few CNAs, with no difference in somatic mutation number. CONCLUSIONS: We conclude that del(17p) has a unique genomic profile and that clonal TP53 mutations, 3p, 4p, or 9p deletions, and genomic complexity are associated with shorter overall survival. Clin Cancer Res; 23(3); 735-45. ©2016 AACR