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Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (<jats:italic>TET2<\/jats:italic>, <jats:italic>DNMT3A<\/jats:italic>) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (<jats:italic>RHOA<\/jats:italic>, <jats:italic>VAV1<\/jats:italic>, <jats:italic>PLCG1, CD28<\/jats:italic>) critical for T\u2010cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T\u2010cell receptor \u03b2 (TRB) rearrangement in 119 AITL, 11 peripheral T\u2010cell lymphomas with T follicular helper phenotype (PTCL\u2010TFH), and 25 PTCL\u2010NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent <jats:italic>TET2<\/jats:italic>, <jats:italic>DNMT3A<\/jats:italic>, and <jats:italic>RHOA<\/jats:italic> mutations in AITL (72%, 34%, 61%) and PTCL\u2010TFH (73%, 36%, 45%) and showed multiple <jats:italic>TET2<\/jats:italic> mutations (2 or 3) in 57% of the involved AITL and PTCL\u2010TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2\u20134) in 18 cases (24%). In selected cases, we confirmed bi\u2010clonal T\u2010cell populations and further demonstrated that these independent T\u2010cell populations harboured identical <jats:italic>TET2<\/jats:italic> mutations by using BaseScope <jats:italic>in situ<\/jats:italic> hybridization, suggesting their derivation from a common <jats:italic>TET2<\/jats:italic> mutant progenitor cell population. Furthermore, both T\u2010cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL\u2010TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common <jats:italic>TET2<\/jats:italic> mutant haematopoietic progenitor pool in AITL and PTCL\u2010TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. \u00a9 2019 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5376","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T06:54:30Z","timestamp":1576824870000},"page":"346-357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Angioimmunoblastic T\u2010cell lymphoma contains multiple clonal T\u2010cell populations derived from a common <i>TET2<\/i> mutant progenitor cell"],"prefix":"10.1002","volume":"250","author":[{"given":"Wen\u2010Qing","family":"Yao","sequence":"first","affiliation":[{"name":"Division of Cellular and Molecular Pathology, Department of Pathology University of Cambridge  Cambridge UK"},{"name":"Department of Pathology West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangtian","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Pathology, Department of Pathology University of Cambridge  Cambridge UK"},{"name":"Department of Haematology Jiangsu Province Hospital, Nanjing Medical University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Sung","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Pathology Chi\u2010Mei Medical Center  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe 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