High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays.
Angioimmunoblastic T-cell lymphoma (AILT) and peripheral T-cell lymphoma, unspecified (PTCL-u) are relatively frequent subtypes of T- or natural killer cell lymphoma. To characterize the structural anomalies of chromosomes associated with these disorders, we here determined chromosome copy number alterations (CNAs) and loss of heterozygosity (LOH) at >55,000 single nucleotide polymorphism loci for clinical specimens of AILT (n=40) or PTCL-u (n=33). Recurrent copy number gain common to both conditions was detected on chromosomes 8, 9 and 19, whereas common LOH was most frequent for a region of chromosome 2. AILT- or PTCL-u-specific CNAs or LOH were also identified at 21 regions, some spanning only a few hundred base pairs. We also identified prognosis-related CNAs or LOH by several approaches, including Cox's proportional hazard analysis. Among the genes that mapped to such loci, a poor prognosis was linked to overexpression of CARMA1 at 7p22 and of MYCBP2 at 13q22, with both genes being localized within regions of frequent copy number gain. For a frequent LOH region at 2q34, we also identified IKAROS family zinc-finger 2 cDNAs encoding truncated proteins. Our data indicate that AILT and PTCL-u consist of heterogeneous subgroups with distinct transforming genetic alterations.
Fujiwara
S-i
SI
Division of Functional Genomics, Jichi Medical University, Tochigi, Japan.
Yamashita
Y
Y
Nakamura
N
N
Choi
Y L
YL
Ueno
T
T
Watanabe
H
H
Kurashina
K
K
Soda
M
M
Enomoto
M
M
Hatanaka
H
H
Takada
S
S
Abe
M
M
Ozawa
K
K
Mano
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000401:mortality; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics
D053468:CARD Signaling Adaptor Proteins; D004268:DNA-Binding Proteins; C111431:IKZF2 protein, human; C116115:MYCBP protein, human; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; D015260:Neprilysin; C426242:CARD11 protein, human; D006162:Guanylate Cyclase