Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

• Published in: Haematologica (Roma) 2016-08, Vol.101 (8), p.959-967
• Main Authors: Sutton, Lesley-Ann, Young, Emma, Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Moysiadis, Theodoros, Plevova, Karla, Rossi, Davide, Kminkova, Jana, Stalika, Evangelia, Pedersen, Lone Bredo, Malcikova, Jitka, Agathangelidis, Andreas, Davis, Zadie, Mansouri, Larry, Scarfò, Lydia, Boudjoghra, Myriam, Navarro, Alba, Muggen, Alice F, Yan, Xiao-Jie, Nguyen-Khac, Florence, Larrayoz, Marta, Panagiotidis, Panagiotis, Chiorazzi, Nicholas, Niemann, Carsten Utoft, Belessi, Chrysoula, Campo, Elias, Strefford, Jonathan C, Langerak, Anton W, Oscier, David, Gaidano, Gianluca, Pospisilova, Sarka, Davi, Frederic, Ghia, Paolo, Stamatopoulos, Kostas, Rosenquist, Richard
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor; Cancer; Chronic lymphocytic leukemia; Complementarity Determining Regions - genetics; Cytogenetic Analysis; Female; Gene Frequency; Gene Rearrangement, B-Lymphocyte; Genes, Immunoglobulin; Genètica mèdica; Hematology; Human health and pathology; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Joining Region - genetics; Immunoglobulin Variable Region - genetics; Leucèmia limfocítica crònica; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Life Sciences; Male; Medical genetics; Medicin och hälsovetenskap; Mutació (Biologia); Mutation; Mutation (Biology); Polymorphism, Single Nucleotide; Prognosis; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - metabolism
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2016.141812

We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P