Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma.
Single-nucleotide polymorphism (SNP) array analysis was performed using the 10K GeneChip array on a series of 26 paired follicular lymphoma (FL) and transformed-FL (t-FL) biopsies and the lymphoma cell lines SCI-1, DoHH2 and RL2261. Regions of acquired homozygosity were detected in 43/52 (83%) primary specimens with a mean of 1.7 and 3.0 aberrations in the FL and t-FL, respectively. A notable feature was the occurrence of recurring sites of acquired uniparental disomy (aUDP) on 6p, 9p, 12q and 17p in cell lines and primary samples. Homozygosity of 9p and 17p arose predominantly in t-FL and in three cases rendered the cell homozygous for a pre-existing mutation of either CDKN2A or TP53. These data suggest that mutation precedes mitotic recombination, which leads to the removal of the remaining wild-type allele. In all, 18 cases exhibited abnormalities in both FL and t-FL samples. In 10 cases blocks of homozygosity were detected in FL that were absent in the subsequent t-FL sample. These differences support the notion that FL and t-FL may arise in a proportion of patients by divergence from a common malignant ancestor cell rather than by clonal evolution from an antecedent FL.
Fitzgibbon
J
J
Cancer Research UK, Centre for Medical Oncology, Barts and the London School of Medicine and Dentistry, London, UK. jude.fitzgibbon@cancer.org.uk
Iqbal
S
S
Davies
A
A
O'shea
D
D
Carlotti
E
E
Chaplin
T
T
Matthews
J
J
Raghavan
M
M
Norton
A
A
Lister
T A
TA
Young
B D
BD
D000328:Adult; D000368:Aged; D002461:Cell Line, Transformed; D002875:Chromosomes; D015894:Genome, Human / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D024182:Uniparental Disomy