title: NOTCH1, TP53, and MAP2K1 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma Are Associated With Progressive Disease.
abstract: Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is considered an indolent neoplasm and its pathogenesis is not well known. We investigated the molecular characteristics of 19 SDRPL patients, 5 of them with progressive disease. IGHV genes were mutated in 9/13 (69%). Cytogenetic and molecular studies identified complex karyotypes in 2 cases, and IGH rearrangements in 3, with PAX5 and potentially TCL1 as partners in each one of them. Copy number arrays showed aberrations in 69% of the tumors, including recurrent losses of 10q23, 14q31-q32, and 17p13 in 3, and 9p21 in 2 cases. Deletion of 7q31.3-q32.3 was present in only 1 case and no trisomies 3 or 18 were detected. NOTCH1 and MAP2K1 were mutated in 2 cases each, whereas BRAF, TP53, and SF3B1 were mutated each in single cases. No mutations were found in NOTCH2 or MYD88. Four of the 5 patients with aggressive disease had mutations in NOTCH1 (2 cases), TP53 (1 case), and MAP2K1 (1 case). The progression-free survival of patients with mutated genes was significantly shorter than in the unmutated (P=0.011). These findings show that SDRPL share some mutated genes but not chromosomal alterations, with other splenic lymphomas, that may confer a more aggressive behavior.
authors.affiliation: *Hospital Clinic, Hematopathology Unit†Department of Anatomic Pathology, Universitat de Barcelona‡Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain§Pathology and Cytopathology Department, Hospital Base Puerto Montt, Puerto Montt, Chile∥Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany¶Royal Marsden Hospital, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez
authors.forename: Alba
authors.initials: A
authors.lastname: Navarro
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martinez-Trillos
authors.forename: Ricardo
authors.initials: R
authors.lastname: Molina-Urra
authors.forename: Blanca
authors.initials: B
authors.lastname: Gonzalez-Farre
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Ferran
authors.initials: F
authors.lastname: Nadeu
authors.forename: Anna
authors.initials: A
authors.lastname: Enjuanes
authors.forename: Guillem
authors.initials: G
authors.lastname: Clot
authors.forename: Dolors
authors.initials: D
authors.lastname: Costa
authors.forename: Ana
authors.initials: A
authors.lastname: Carrio
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.forename: Susanne
authors.initials: S
authors.lastname: Bens
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Andrew
authors.initials: A
authors.lastname: Wotherspoon
authors.forename: Sílvia
authors.initials: S
authors.lastname: Beà
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002677:Chile; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D015321:Gene Rearrangement; D050438:Genes, Immunoglobulin Heavy Chain; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D051881:Receptor, Notch1 / Q000235:genetics*; D012307:Risk Factors; D013160:Splenic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human