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@ARTICLE{MerkAhmad:277132,
      author       = {K. Merk-Ahmad and J. Bein and S. Scharf and H. Schäfer and
                      T. Bexte and E. Ullrich$^*$ and A. G. Loth and N. Flinner
                      and T. Senff and O. Schneider and M.-L. Hansmann and M. Piel
                      and B. Häupl$^*$ and T. Oellerich and E. Donnadieu and S.
                      Hartmann},
      title        = {{T}he {RHOA} {M}utation {G}17{V} {D}oes {N}ot {L}ead to
                      {I}ncreased {M}igration of {H}uman {M}alignant {T} {C}ells
                      but {I}s {A}ssociated with {M}atrix {R}emodelling.},
      journal      = {Cancers},
      volume       = {15},
      number       = {12},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-01294},
      pages        = {3226},
      year         = {2023},
      abstract     = {Nodal T-follicular helper cell lymphoma,
                      angioimmunoblastic-type (AITL), is characterized by
                      constitutional symptoms, advanced-stage disease, and
                      generalized lymphadenopathy. A genetic hallmark of this
                      lymphoma is the frequent occurrence of the RHOA mutation
                      G17V in neoplastic cells, which is observed in around $60\%$
                      of patients. Because RHOA is involved in both T-cell
                      receptor downstream signalling and cell migration, we
                      hypothesized that the characteristic presentation of AITL
                      could be the result of enhanced tumor cell migration.
                      Therefore, this study aimed to elucidate the impact of the
                      RHOA variant G17V on the migration of neoplastic T cells. We
                      transfected the T-cell lymphoma cell lines HH and HuT78 to
                      stably express the RHOA-G17V variant. RHOA-G17V-expressing T
                      cells did not exhibit enhanced motility compared to
                      empty-vector-transfected cells in microchannels, a 3D
                      collagen gel, or primary human lymphatic tissue. Cells of
                      the HH cell line expressing RHOA-G17V had an increased
                      number of cells with cleaved collagen compared with the
                      empty-vector-transfected cells. Therefore, we hypothesized
                      that the early spread of AITL tumor cells may be related to
                      remodelling of the extracellular matrix. Accordingly, we
                      observed a significant negative correlation between the
                      relative area of collagen in histological sections from 18
                      primary AITL and the allele frequency of the RHOA-G17V
                      mutation. In conclusion, our results suggest that the
                      characteristic presentation of AITL with early, widespread
                      dissemination of lymphoma cells is not the result of an
                      enhanced migration capacity due to the RHOA-G17V mutation;
                      instead, this feature may rather be related to extracellular
                      matrix remodelling.},
      keywords     = {RHOA mutation G17V (Other) / angioimmunoblastic T-cell
                      lymphoma (Other) / live cell imaging (Other) / movement
                      (Other)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37370838},
      doi          = {10.3390/cancers15123226},
      url          = {https://inrepo02.dkfz.de/record/277132},
}