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Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with isolated trisomy 12 or associated with other chromosomal alterations
Author(s) -
López Cristina,
Delgado Julio,
Costa Dolors,
Conde Laura,
Ghita Gabriela,
Villamor Neus,
Navarro Alba,
Cazorla Maite,
Gómez Cándida,
Arias Amparo,
Muñoz Concha,
Baumann Tycho,
Rozman María,
Aymerich Marta,
Colomer Dolors,
Cobo Francesc,
Campo Elías,
LópezGuillermo Armando,
Montserrat Emili,
Carrió Ana
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.21972
Subject(s) - trisomy , chronic lymphocytic leukemia , trisomy 8 , cytogenetics , biology , aneuploidy , leukemia , medicine , genetics , chromosome , gene
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. © 2012 Wiley Periodicals, Inc.