Whole-Genome Analysis and HLA Genotyping of Enteropathy-Type T-Cell Lymphoma Reveals 2 Distinct Lymphoma Subtypes

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

“…It has been reported that EATL is characterized by recurrent gains of 1q, 5q, 7q, and recurrent losses of 8p, 9p, and 13q, with gains of 9q33-q34 being the most frequent alteration (60% of frequency). 15 In line with those previous findings, the present series of EATL was characterized by multiple common and distinct imbalances. In contrast to other types of tumors, the EATL profile did not have a single or unique alteration, but rather have multiple regions, an observation that supports the view that EATL is a multifactorial and polygenic (complex) disorder.…”

“…We demonstrated a large number of genetic abnormalities in our Type II EATLs: gains of 1q, 5q, 7q, and 9q, and losses of 8p, 9p, and 13q, with the most common gain of 9q33-q34 (58%). The general profile is in concordance with previously reported data from BAC-arrays of Deleeuw et al 15 Our highresolution array comparative genomic hybridization and expanded FISH analysis in a series of EATL Type II in Japan has identified a genomic profile similar to EATL of Western countries with characteristics of both Types I and II. Despite that our cases are phenotypically more similar to EATL Type II the histology of the tumor cells is more heterogeneous and range from small to large; and the genomic profile lacks the EATL Type II characteristic genomic copy number gain of MYC oncogene locus at 8q24 but has the 1q32 and 5q34 gains previously described as characteristic of EATL Type I.…”

“…Therefore, we propose that gain of 9q34 is frequent in Japanese EATL cases, similar to the European series. 14,15 Among other important gene targets, the target gene CARD9 was selected for FISH validation in the 9q34 region. CARD9 is an oncogene regulator of the ITAM-mediated signaling pathway, forming a complex with BCL10-MALT1, and is a regulatory mechanism for NFKB and MAPK activation through innate and adaptive immunereceptors.…”

“…All alterations were confirmed by visual inspection by two different observers. Regions of alterations (ROAs) were identified as previously described by Deleeuw et al 15 based on the frequency and exclusivity of genes or losses and the minimal common regions identified. The Waves array comparative genomic hybridization Correction Algorithm (WACA), based on GC content and fragment size adjustment was applied in several cases.…”

“…14 A recent study of western EATL has reported frequent complex gains of 9q31.3-qter (70%) and loss of 16q12.1 (23%); and the subtype of EATL Type I was characterized by gains of 1q and 5q, while Type II EATL was associated with gains in 8q. 15 In Japan, one study using comparative genomic hybridization analysis identified gains of 8q2 (47%), Xp (53%), and Xq (73%), but none of the cases had any gains of 1q3, 5q3, 7q2, or 9q3, which are typically found in Caucasian EATL patients. 6 To the best of our knowledge, there have been no reports on the association between αβ-and γδ-T-cell phenotype markers and genomic alterations.…”