Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma.
Aggressive adult T-cell leukemia/lymphoma (ATLL) such as acute and lymphoma types are fatal diseases with poor prognosis. Although these 2 subtypes feature different clinicopathologic characteristics, no detailed comparative analyses of genomic/genetic alterations have been reported. We performed array-based comparative genomic hybridization for 17 acute and 49 lymphoma cases as well as real-time quantitative polymerase chain reaction (PCR) to identify the target genes of recurrently amplified regions. Comparison of the genome profiles of acute and lymphoma types revealed that the lymphoma type had significantly more frequent gains at 1q, 2p, 4q, 7p, and 7q, and losses of 10p, 13q, 16q, and 18p, whereas the acute type showed a gain of 3/3p. Of the recurrent high-level amplifications found at 1p36, 6p25, 7p22, 7q, and 14q32 in the lymphoma type, we were able to demonstrate that CARMA1 is a possible target gene of the 7p22 amplification for the lymphoma type but not for the acute type. Furthermore, we found BCL11B overexpression in the acute type regardless of the 14q32 gain/amplification, but no or low expression of the gene in the lymphoma type. These results suggest that acute and lymphoma types are genomically distinct subtypes, and thus may develop tumors via distinct genetic pathways.
Division of Molecular Medicine, Aichi Cancer Center Institute, Nagoya, Aichi, Japan.
Aya
A
Oshiro
Hiroyuki
H
Tagawa
Koichi
K
Ohshima
Kennosuke
K
Karube
Naokuni
N
Uike
Yukie
Y
Tashiro
Atae
A
Utsunomiya
Masato
M
Masuda
Nobuyuki
N
Takasu
Shigeo
S
Nakamura
Yasuo
Y
Morishima
Masao
M
Seto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins; D002875:Chromosomes; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006162:Guanylate Cyclase / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C479740:BCL11B protein, human; D053468:CARD Signaling Adaptor Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C426242:CARD11 protein, human; D006162:Guanylate Cyclase