{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:16:39Z","timestamp":1762506999966,"version":"3.37.3"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T00:00:00Z","timestamp":1484006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Dermatology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (<jats:styled-content style=\"fixed-case\">GIST<\/jats:styled-content>s) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in <jats:italic>c\u2010kit<\/jats:italic> (most commonly), platelet\u2010derived growth factor receptor A, neurofibromatosis\u20101, and succinate dehydrogenase genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We report on molecular characterization and tumor histopathology of two siblings in whom lentigines and caf\u00e9\u2010au\u2010lait macules were present along with multifocal <jats:styled-content style=\"fixed-case\">GIST<\/jats:styled-content>. Immuhistochemical analysis of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>34 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>117 was performed on <jats:styled-content style=\"fixed-case\">GIST<\/jats:styled-content> biopsy samples from both siblings, while <jats:italic>c\u2010kit<\/jats:italic> mutational analysis was done by <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and direct sequencing on <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> from peripheral blood leukocytes of all family members and from paraffin\u2010embedded gastric biopsy specimens of affected siblings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Histopathology revealed positive expression of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>117 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>34. Mutational analysis showed the germline c.1676T&gt;C mutation in <jats:italic>c\u2010kit<\/jats:italic> exon 11, (p.(Val559Ala)), in the peripheral blood of both siblings and a second exon 11 mutation, c.1669T&gt;A (p.(Trp557Arg)) in the tumor biopsy of one of them. Initiation of imatinib treatment resulted in striking resolution of their hyperpigmentation and a stable gastrointestinal disease in one of them.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A <jats:italic>c\u2010kit<\/jats:italic> mutational test in familial <jats:styled-content style=\"fixed-case\">GIST<\/jats:styled-content>s is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijd.13516","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T10:07:50Z","timestamp":1484302070000},"page":"195-201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Familial gastrointestinal stromal tumors, lentigines, and caf\u00e9\u2010au\u2010lait macules associated with germline <i>c\u2010kit<\/i> mutation treated with imatinib"],"prefix":"10.1111","volume":"56","author":[{"given":"Divya","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Dermatology and STD Jawaharlal Institute of Postgraduate Medical Education &amp; 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