The authors have no conflicts of interest to disclose. Any data not presented in the manuscript can be made available upon reasonable request to the authors. Table S1. Summary of the basic characteristics of the study cohort. AITL diagnosis was established adopting a combination of World Health Organization (WHO) and International Consensus Classification (ICC), including morphological features and the expression of at least two TFH markers (PD1/CXCL13/ICOS/CD10 and/or BCL6) in CD3/CD4-positive neoplastic cells. Immunohistochemical studies for CD8/CD20/CD23/CD21 and CD138 as well as in situ hybridization for Epstein–Barr virus-encoded RNA (EBER) were also performed. The frequency of EBER-positive cells was semi-quantitatively classified into four groups (0, absence; 1, ≥2 cells; 2, >10%–25% cells; and 3, >25%). NA, not available. Table S2. Custom SureSelect target enrichment panel assays used for next generation sequencing (NGS). The panel comprised 158 genes. Captured libraries were processed using a Magnis SureSelect XT HS kit (Agilent Technologies, Santa Clara, CA, USA) and sequenced on a NextSeq500 platform (Illumina Inc., San Diego, CA, USA). Table S3. Summary of variants found in sequenced solid malignancies. Table S4. Summary of validation cohort characteristics (n = 14). Four of the 14 AITL patients presented solid tumour (4/14, 28.47%), all before AITL onset. Seven of the 14 harboured DNMT3A mutations (50%). Three of the four cases with solid malignancies presented DNMT3A variants (75%), and four of the remaining cases without solid tumour (4/10, 40%) harboured them. Two of the three cases with additional solid malignancies and harbouring DNMT3A variants presented them outside the C5-MT domain. Moreover, three of the four cases with solid tumour harboured more than one CHIP mutation. Figure S1. Localization of the variants found in the DNMT3A gene. Figure S2. Comparison of Kaplan–Meier curves for overall survival (OS) and progression-free survival (PFS): A and B, between cases with negative/low levels of expression of Epstein–Barr virus-encoded RNA (EBER) (EBV 0–1) and cases with moderate/high expression levels of EBER (EBV 2–3); C and D, between early-relapsed (POD24 yes) and non-early-relapsed (POD24 no) patients; E and F, between AITL patients with or without solid tumour(s); G and H, between AITL cases with AITL onset after the occurrence of a solid tumour and all other patients; I and J, classifying patients by CHIP (no CHIP mutations, CHIP mutations + AITL onset after solid tumour and the all other cases with CHIP variants). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Dıáz-Alejo et al. (Sun,) studied this question.