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

• Published in: Leukemia Vol. 22; no. 10; pp. 1891 - 1898
• Main Authors: FUJIWARA, S-I, YAMASHITA, Y, TAKADA, S, ABE, M, OZAWA, K, MANO, H, NAKAMURA, N, CHOI, Y. L, UENO, T, WATANABE, H, KURASHINA, K, SODA, M, ENOMOTO, M, HATANAKA, H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.10.2008; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Anomalies; Arrays; Biological and medical sciences; CARD Signaling Adaptor Proteins - genetics; Care and treatment; Chromosome 13; Chromosome 2; Chromosome Aberrations; Chromosomes; Copy number; Diagnosis; DNA microarrays; DNA-Binding Proteins - genetics; Female; Genes; Genetic aspects; Genomes; Genomics; Guanylate Cyclase - genetics; Hazard assessment; Hematologic and hematopoietic diseases; Heterozygosity; Humans; Hybridization; Ikaros protein; Ikaros Transcription Factor - genetics; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Loci; Loss of Heterozygosity; Lymphocytes T; Lymphoma; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - mortality; Lymphoma, T-Cell, Peripheral - genetics; Lymphoma, T-Cell, Peripheral - mortality; Male; Medical prognosis; Medical sciences; Middle Aged; Natural killer cells; Neprilysin - analysis; Nucleotides; Oligonucleotide Array Sequence Analysis; Pathogenesis; Pathology; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Subgroups; T cell lymphoma; Transcription Factors - genetics; Zinc finger proteins; Japan; United States > US; High resolution; Allelic imbalance; Angioimmunoblastic T cell lymphoma; Typing; Genetic variability; Hematology; T lymphoma; Copy number; Chromosome number; Genotype; Malignant hemopathy; Non Hodgkin lymphoma; IKZF2; chromosome copy number alterations; Peripheral T cell lymphoma; Lymphoproliferative syndrome; Loss of heterozygosity; Single nucleotide polymorphism; T-cell lymphoma; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2008.191

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.