title: Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with isolated trisomy 12 or associated with other chromosomal alterations.
abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries. Chromosomal abnormalities commonly found using conventional cytogenetics and FISH are del(11)(q22-23), trisomy 12, del(13)(q14), and del(17)(p13). Trisomy 12 is the most frequent numerical abnormality in CLL. It can appear isolated or associated with other chromosomal aberrations, including t(14;18)(q32;q21) and trisomy 18. The aim of this study was to determine whether CLL patients with isolated trisomy 12 or associated with other chromosomal alterations have different clinico-pathological features, including a different distribution NOTCH1 mutation. Patients were classified into four groups: Group 1, isolated trisomy 12 (n=14); Group 2, trisomy 12 plus trisomy 18 (n=4); Group 3, trisomy 12 plus t(14;18) (n=8); and Group 4: patients with trisomy 12 plus other abnormalities not involving BCL2 (n=28). The Binet stage and expression of ZAP70 were significantly different among cytogenetic groups. NOTCH1 mutations were detected in 6/12 (50%) patients from Group 1, 4/25 (16%) patients from Group 4, and in no patient from groups 2 and 3 (P=0.020). Patients in Group 2 had a more rapid disease progression (median Treatment-free Survival 2 months) as against patients from Groups 1 (50 months), 3 (69 months), or 4 (68 months; P=0.001). These findings indicate that the distribution of NOTCH1 mutations in CLL with trisomy 12 is heterogeneous and that the presence of additional chromosomal abnormalities such as trisomy 18 could change the prognosis of these patients.
authors.affiliation: Hematopathology Unit, Pathology Department, Hospital Clínic, Institut d'Investigacions Biomédiques Agustí Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: López
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.forename: Dolors
authors.initials: D
authors.lastname: Costa
authors.forename: Laura
authors.initials: L
authors.lastname: Conde
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ghita
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Alba
authors.initials: A
authors.lastname: Navarro
authors.forename: Maite
authors.initials: M
authors.lastname: Cazorla
authors.forename: Cándida
authors.initials: C
authors.lastname: Gómez
authors.forename: Amparo
authors.initials: A
authors.lastname: Arias
authors.forename: Concha
authors.initials: C
authors.lastname: Muñoz
authors.forename: Tycho
authors.initials: T
authors.lastname: Baumann
authors.forename: María
authors.initials: M
authors.lastname: Rozman
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Francesc
authors.initials: F
authors.lastname: Cobo
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Ana
authors.initials: A
authors.lastname: Carrió
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D016133:Polymerase Chain Reaction; D011379:Prognosis; D051881:Receptor, Notch1 / Q000235:genetics*; D015996:Survival Rate; D014314:Trisomy / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1