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@ARTICLE{Polubothu:600684,
      author       = {Polubothu, Satyamaanasa and Bender, Nicole and Muthiah,
                      Siobhan and Zecchin, Davide and Demetriou, Charalambos and
                      Martin, Sara Barberan and Malhotra, Sony and Travnickova,
                      Jana and Zeng, Zhiqiang and Böhm, Markus and Barbarot,
                      Sebastien and Cottrell, Catherine and Davies, Olivia and
                      Baselga, Eulalia and Burrows, Nigel P. and Carmignac,
                      Virginie and Diaz, Joey Santiago and Fink, Christine and
                      Haenssle, Holger A. and Happle, Rudolf and Harland, Mark and
                      Majerowski, Jacquelyn and Vabres, Pierre and Vincent, Marie
                      and Newton-Bishop, Julia A. and Bishop, D. Tim and Siegel,
                      Dawn and Patton, E. Elizabeth and Topf, Maya and Rajan, Neil
                      and Drolet, Beth and Kinsler, Veronica A.},
      title        = {{PTPN}11 {M}osaicism {C}auses a {S}pectrum of {P}igmentary
                      and {V}ascular {N}eurocutaneous {D}isorders and
                      {P}redisposes to {M}elanoma},
      journal      = {The journal of investigative dermatology},
      volume       = {143},
      number       = {6},
      issn         = {0022-202X},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {PUBDB-2023-08102},
      pages        = {1042 - 1051.e3},
      year         = {2023},
      abstract     = {Phakomatosis pigmentovascularis is a diagnosis that denotes
                      the coexistence of pigmentary and vascular birthmarks of
                      specific types, accompanied by variable multisystem
                      involvement, including CNS disease, asymmetrical growth, and
                      a predisposition to malignancy. Using a tight phenotypic
                      group and high-depth next-generation sequencing of affected
                      tissues, we discover here clonal mosaic variants in gene
                      PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis
                      pigmentovascularis type III or spilorosea. Within an
                      individual, the same variant is found in distinct pigmentary
                      and vascular birthmarks and is undetectable in blood. We go
                      on to show that the same variants can cause either the
                      pigmentary or vascular phenotypes alone, and drive melanoma
                      development within pigmentary lesions. Protein structure
                      modeling highlights that although variants lead to loss of
                      function at the level of the phosphatase domain, resultant
                      conformational changes promote longer ligand binding. In
                      vitro modeling of the missense variants confirms downstream
                      MAPK pathway overactivation and widespread disruption of
                      human endothelial cell angiogenesis. Importantly, patients
                      with PTPN11 mosaicism theoretically risk passing on the
                      variant to their children as the germline RASopathy Noonan
                      syndrome with lentigines. These findings improve our
                      understanding of the pathogenesis and biology of nevus
                      spilus and capillary malformation syndromes, paving the way
                      for better clinical management.},
      cin          = {CSSB-LIV/UKE-MT},
      ddc          = {610},
      cid          = {$I:(DE-H253)CSSB-LIV_UKE-MT-20220525$},
      pnm          = {899 - ohne Topic (POF4-899) / ZF-MEL-CHEMBIO - Chemical
                      Biology in Zebrafish: Drug-Leads and New Targets in the
                      Melanocyte Lineage and Melanoma (648489)},
      pid          = {G:(DE-HGF)POF4-899 / G:(EU-Grant)648489},
      experiment   = {EXP:(DE-MLZ)NOSPEC-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36566878},
      UT           = {WOS:001010699700001},
      doi          = {10.1016/j.jid.2022.09.661},
      url          = {https://bib-pubdb1.desy.de/record/600684},
}