Volume 132, Issue 5, Pages 1902-1911 (May 2007) Whole-Genome Analysis and HLA Genotyping of Enteropathy-Type T-Cell Lymphoma Reveals 2 Distinct Lymphoma Subtypes  Ronald J. deLeeuw, Andreas Zettl, Erdwine Klinker, Eugenia Haralambieva, Magan Trottier, Raj Chari, Yong Ge, Randy D. Gascoyne, Andreas Chott, Hans–Konrad Müller–Hermelink, Wan L. Lam  Gastroenterology  Volume 132, Issue 5, Pages 1902-1911 (May 2007) DOI: 10.1053/j.gastro.2007.03.036 Copyright © 2007 AGA Institute Terms and Conditions

Figure 1 Whole-genome SeeGH karyogram of ETL sample 30 vs reference DNA. Expanded view of chromosome arm 1q, 9q, and 14q with annotation of copy number loss, normal copy number, copy number gain, high-level gain, and T-cell–receptor gene rearrangement. Each dot represents data from 1 BAC-derived segment on the array. Data points to the left and right of the center line represent genetic losses and gains, respectively. Lines at Log2 ratios of −0.5 and +0.5 are scale bars only. Gastroenterology 2007 132, 1902-1911DOI: (10.1053/j.gastro.2007.03.036) Copyright © 2007 AGA Institute Terms and Conditions

Figure 2 Summary of chromosomal imbalances detected by tiling-path array CGH in 30 ETL samples. Green lines on the left side of the ideogram indicate loss of chromosomal material; red lines on the right side indicate a gain of chromosomal material. High-frequency small losses at 7q34 and 14q11.2 are caused by TCR gene rearrangement. 15q11.2 contains a natural copy number polymorphism. Gastroenterology 2007 132, 1902-1911DOI: (10.1053/j.gastro.2007.03.036) Copyright © 2007 AGA Institute Terms and Conditions

Figure 3 Recurrent gains and losses in ETL. Chromosome 9q gains were found in all morphologic subtypes of ETL. However, 9q31.3-33.2 gains were predominantly absent in ETL with 16q12.1 losses (P < .01). Gains of 1q32.2-q41 and 5q34-q35.2 and those of 7q11.23-q21.3 and 8q13.3-q21.11 tended to occur within the same samples (P < .01). Compared with nonmonomorphic ETL, monomorphic ETL was associated with a significantly more frequent gain of 8q22.2-q24.3 and less frequent gains of 1q32.2-q41 and 5q34-q35.2. Bold entries identify novel regions of alteration; black squares, copy number gain of region; grey squares, copy number loss of region; g, gain of chromosomal material; d, loss of chromosomal material. Gastroenterology 2007 132, 1902-1911DOI: (10.1053/j.gastro.2007.03.036) Copyright © 2007 AGA Institute Terms and Conditions

Figure 4 ETL are characterized by highly recurrent gains of 9q and losses of 16q that are commonly exclusive. (A) Sample 8 showing a gain of 9q22.33-qter without 16q loss. (B) Sample 18 showing normal copy number of chromosome 9q with 16q11.2-q22.1 loss. Each dot represents data from 1 BAC-derived segment on the array. Data points to the left and right of the center line represent genetic losses and gains, respectively. Lines at Log2 ratios of −0.5 and +0.5 are scale bars only. Gastroenterology 2007 132, 1902-1911DOI: (10.1053/j.gastro.2007.03.036) Copyright © 2007 AGA Institute Terms and Conditions

Figure 5 Principle component analysis of ROA in 30 ETL samples. (A) Plot of samples along principal components 2 and 3. (B) Plot of components along principal components 2 and 3. Solid circles denote type 1 ETL, hollow circles denote type 2 ETL. (A) Separation between top left and bottom right for the distinct subtypes of ETL were influenced most by 1q32.2-q41 (upper arrow) in top right and 8q13.3-q21.11/8q22.1-q24.3 (lower arrow) in bottom left of B. Gastroenterology 2007 132, 1902-1911DOI: (10.1053/j.gastro.2007.03.036) Copyright © 2007 AGA Institute Terms and Conditions

Figure 6 Frequency distribution of HLA-DQB1 genotypes in types 1 and 2 ETL. Distribution of HLA-DQB1*02 heterozygous/homozygous, HLA-DQ*0302, and non-DQB1*02/DQB1*0302 in this study as compared with previously published unclassified ETL and healthy Caucasian controls.8 Gastroenterology 2007 132, 1902-1911DOI: (10.1053/j.gastro.2007.03.036) Copyright © 2007 AGA Institute Terms and Conditions

Figure 7 Proposed subdivision of ETL based on clinical, morphologic, immunophenotypical, genetic, and HLA genotype features. Gastroenterology 2007 132, 1902-1911DOI: (10.1053/j.gastro.2007.03.036) Copyright © 2007 AGA Institute Terms and Conditions