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Publication Detail
Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Dobson R, Du PY, RĂ¡so-Barnett L, Yao WQ, Chen Z, Casa C, EI-Daly H, Farkas L, Soilleux E, Wright P, Grant JW, Rodriguez-Justo M, Follows GA, Rashed H, Fabre M, Baxter EJ, Vassiliou G, Wotherspoon A, Attygalle AD, Liu H, Du MQ
  • Publication date:
  • Pagination:
    489, 499
  • Journal:
  • Volume:
  • Issue:
  • Status:
  • Print ISSN:
Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) are a group of complex clinicopathological entities that originate from T follicular helper cells and share a similar mutation profile. Their diagnosis is often a challenge, particularly at an early stage, because of a lack of specific histological and immunophenotypic features, paucity of neoplastic T cells and prominent polymorphous infiltrate. We investigated whether the lymphoma-associated RHOA Gly17Val (c.50G>T) mutation, occurring in 60% of cases, is present in the early "reactive" lesions, and whether mutation analysis could help to advance the early diagnosis of lymphoma. The RHOA mutation was detected by quantitative polymerase chain reaction with a locked nucleic acid probe specific to the mutation, and a further peptide nucleic acid clamp oligonucleotide to suppress the amplification of the wild-type allele. The quantitative polymerase chain reaction assay was highly sensitive and specific, detecting RHOA Gly17Val at an allele frequency of 0.03%, but not other changes in Gly17, nor in 61 controls. Among the 37 cases of AITL and PTCL-TFH investigated, RHOA Gly17Val was detected in 62.2% (23/37) of which 19 had multiple biopsies including preceding biopsies in ten and follow-up biopsies in 11 cases. RHOA Gly17Val was present in each of these preceding or follow-up biopsies including 18 specimens that showed no evidence of lymphoma by combined histological, immunophenotypic and clonality analyses. The mutation was seen in biopsies 0-26.5 months (mean 7.87 months) prior to the lymphoma diagnosis. Our results show that RHOA Gly17Val mutation analysis is valuable in the early detection of AITL and PTCL-TFH.
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