Overview of non‐coding mutations in chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia type in which the genetic alterations influencing the clinico‐biological course are not entirely understood. CLL has a heterogeneous course, with some patients showing an indolent course and others experiencing an aggressive course. Whole‐genome sequencing and whole‐exome sequencing studies identified recurrently mutated genes in CLL and profiled its clonal evolution patterns. However, more recent whole‐genome sequencing studies also identified variants in non‐coding sequences of the CLL genome, revealing important lesions outside the protein‐coding regions. Here we describe the most representative non‐coding lesion of the CLL genome, including lesions in the 3′‐UTR region of NOTCH1 which result in the truncation of the NOTCH1 protein PEST domain, and non‐coding mutations in an enhancer region on chromosome 9p13 which result in reduced expression of the PAX5 transcription factor. In addition, we describe the role of microRNA in CLL, in particular the miR15a/miR16‐1 microRNA recurrently affected by deletions of chromosome 13q14. Together, new findings in non‐coding genome genetic lesions provide a more complete portrait of the genomic landscape of CLL with clinical implications.

Leukemia multiclass assessment and classification from Microarray and RNA-seq technologies integration at gene expression level

“…It this disease, the genetic alterations have a great impact on the clinical course of the patients. Previous whole genome and exome sequencing studies have reveled recurrently mutated genes (such as NOTCH1, MYD88, TP53, ATM, SF3B1, FBXW7, POT1, CHD2, RPS15, IKZF3, ZNF292, ZMYM3, ARID1A, and PTPN11), but deletions of chromosome 13q14 is the most frequent aberration in CLL, occurring in 55% of cases [82].…”

Polymorphisms in eicosanoid‐related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti‐inflammatory drug hypersensitivity

“…In general, there is not much information about the variants we found to be associated with NSAID hypersensitivity in other human diseases. Several variants in PTGS1 have been clinically associated with different inflammatory pathologies, including cardiovascular diseases, ischaemic stroke, multiple cancers and antiplatelet therapy resistance 32–37 . The rs10306194 polymorphism in PTGS1 has been associated with breast cancer, 38 and, in 2017, it was described as part of a haplotype block associated with a risk of acute myeloid leukaemia; 39 however, its functional relevance needs to be clarified.…”

“…Several variants in PTGS1 have been clinically associated with different inflammatory pathologies, including cardiovascular diseases, ischaemic stroke, multiple cancers and antiplatelet therapy resistance. [32][33][34][35][36][37] The rs10306194 polymorphism in PTGS1 has been associated with breast cancer, 38 and, in 2017, it was described as part of a haplotype block associated with a risk of acute myeloid leukaemia; 39 however, its functional relevance needs to be clarified. Although several SNPs in the 3´-UTR of PTGS1 have been identified, appearing at high frequencies in some cases, very few have been evaluated with regard to potential clinical associations.…”

The noncoding RNA revolution—three decades and still going strong!

“…The review by Spina and Rossi gives an overview of the mutation landscape in the most frequent type of human leukemia, chronic lymphocytic leukemia, with a particular focus on noncoding lesions of the genome (Spina and Rossi, ).…”