Multicolour fluorescence in situ hybridization analysis of t(14;18)-positive follicular lymphoma and correlation with gene expression data and clinical outcome.
In order fully to identify secondary chromosomal alterations, such as duplications, additions and marker chromosomes that remained unresolved by G banding, 60 cases of t(14;18)-positive follicular lymphoma (FL) were analysed by multicolour karyotyping techniques [multicolour fluorescence in situ hybridization (MFISH)/multicolour banding for chromosome 1 (MBAND1)]. A total of 165 additional structural chromosomal aberrations were delineated. An increased frequency of chromosomal gains involving X, 1q, 2, 3q27-q29, 5, 6p11-p21, 7, 8, 11, 12, 14q32, 17q, 18 and 21 and deletions of 1p36, 3q28-q29, 6q, 10q22-q24 and 17p11-p13 was revealed by the MFISH/MBAND1 analysis. Balanced translocations other than t(14;18) were uncommon, whereas unbalanced translocations were numerous. Deletion of 1p36 and duplication of 1p33-p35, 1p12-p21 and 1q21-q41 were regularly involved in chromosome 1 alterations, seen in 53% of the cases. A strong correlation was demonstrated between gains of individual chromosomal bands and increased gene expression, including 1q22/MNDA, 6p21/CDKN1A, 12q13-q14/SAS, 17q23/ZNF161, 18q21/BCL2 and Xq13/IL2RG. Unfavourable overall survival was associated with del(1)(p36) and dup(18q). These data support the notion that translocation events are primarily responsible for FL disease initiation, whereas the unbalanced chromosomal gains and losses that mirror the gene expression patterns characterize clonal evolution and disease progression, and thus provide further insights into the biology of FL.
Lestou
Valia S
VS
Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada. vlestou@bccancer.bc.ca
Gascoyne
Randy D
RD
Sehn
Laurie
L
Ludkovski
Olga
O
Chhanabhai
Mukesh
M
Klasa
Richard J
RJ
Husson
Hervé
H
Freedman
Arnold S
AS
Connors
Joseph M
JM
Horsman
Douglas E
DE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014178:Translocation, Genetic