High prevalence of MAP2K1 mutations in variant and IGHV4-34–expressing hairy-cell leukemias

DriverFinder: A Gene Length-Based Network Method to Identify Cancer Driver Genes

“…For example, TTN, the longest gene in human genome, accumulates many variants just due to its length [24,26]. TTN may be selected in many computational methods; however, it usually serves as passenger gene [27]. This phenomenon indicates that many current methods have a strong preference towards identifying long genes [24].…”

Molecular lesions of signalling pathway genes in clonal B‐cell lymphocytosis with marginal zone features

“…Though the small number of cases prevents statistically supported conclusions, NOTCH2 mutations tended to cluster with cases showing an intrasinusoidal pattern of BM infiltration (28%; 95% CI: 7-64%; 2/7 vs. 0%; 95% CI: 0-34%; 0/9; P = 0Á21), while MYD88 mutations tended to be enriched in cases secreting an IgM monoclonal component (50%; 95% CI: 15-85%; 2/4 vs. 16%; 95% CI: 3-46%; 2/12; P = 0Á21) (Table SI). CBL-MZ lacked MAP2K1 mutations, which are recurrent in up to 50% SLLU (Waterfall et al, 2014).…”

“…If CBL-MZ are to be considered the early stage of SMZL, they should share a common genetic profile with this lymphoma, including recurrent NOTCH2 mutations and, more generally, mutually exclusive lesions affecting signalling pathways involved in normal MZ differentiation (Kiel et al, 2012;Rossi et al, 2012;Parry et al, 2013;Mart ınez et al, 2014). Otherwise, if CBL-MZ represent the early phase of a SLLU, they might harbour MAP2K1 mutations and lack lesions of MZ differentiation genes (Waterfall et al, 2014).…”

“…If CBL-MZ are to be considered the early stage of SMZL, they should share a common genetic profile with this lymphoma, including recurrent NOTCH2 mutations and, more generally, mutually exclusive lesions affecting signalling pathways involved in normal MZ differentiation (Kiel et al, 2012;Rossi et al, 2012;Parry et al, 2013;Mart ınez et al, 2014). Otherwise, if CBL-MZ represent the early phase of a SLLU, they might harbour MAP2K1 mutations and lack lesions of MZ differentiation genes (Waterfall et al, 2014).To unravel the genetics of CBL-MZ, mutations of the NOTCH2, NOTCH1, BIRC3, TNFAIP3, TRAF3, IKBKB, MYD88, CD79A, CD79B, CARD11, BRAF and MAP2K1 genes were investigated on peripheral blood (PB) samples (tumour representation >50%) from 16 CBL-MZ identified according to the criteria defined by Xochelli et al (2014), namely: (i) persistent monoclonal B-cell lymphocytosis in the PB; (ii) immnophenotypic features consistent with a MZ lymphoproliferation, including lack of CD5, CD10, and CD103 expression and a Matutes score <2; (iii) bone marrow (BM) infiltration by small lymphocytes with no or limited plasmacytic differentiation; (iv) absence of lymphadenopathy, splenomegaly or extranodal tissue organomegaly by computerized tomography scan. BM biopsies were reviewed by experienced haematopathologists.…”

Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment

“…Using WES, activating mutations in the mitogen‐activated protein kinase 1 ( MAP2K1) gene (15q22.1‐q22.3) were found in VH4–34 positive HCL (5/7 pts) and HCL‐V (CD103+, CD25‐) that were either IGHV4–34 negative (6/15 pts) or IGHV4–34 positive HCL‐V (4/9 pts). In contrast, MAP2K1 mutations were identified in only 1/20 cases of IGHV4–34 negative HCL patients 21. In HCL‐V, the identification of MAP2K1 mutations is an argument that supports the diagnosis but its presence is detected in only 50% of cases.…”