Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors.
- 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 López, Alba
- Muggen, Alice F.
- Yan, Xiao-Jie
- Nguyen-Khac, Florence
- Larrayoz, Marta
- Panagiotidis, Panagiotis
- Chiorazzi, Nicholas
- Utoft Niemann, Carsten
- Belessi, Chrysoula
- Campo Güerri, Elias
- Strefford, Jonathan C.
- Langerak, Anton W.
- Oscier, David
- Gaidano, Gianluca
- Pospisilova, Sarka
- Davi, Frederic
- Ghia, Paolo
- Stamatopoulos, Kostas
- Rosenquist, Richard
DOIAbstract
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<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hyp...
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