PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor

PDGFRA-mutant syndrome

“…3,9,10,15 In the family reported by Chompret et al 10 a D846Y PDGFRA exon 18 mutation cosegregated with well documented GISTs (CD117 + , CD34 + ). An individual bearing a germline V561D PDGFRA exon 12 mutation (family was unavailable for studies) displayed multiple gastric GISTs, and gastrointestinal fibrous tumors and lipomas.…”

“…This hypothesis is also supported by the frequent detection of diffuse interstitial Cajal cell hyperplasia in germline KIT mutations 5 but not in germline PDGFRA mutations; in fact, not only did we fail to find diffuse interstitial Cajal cell hyperplasia in any of the mutant individuals of the kindred herein reported, but diffuse interstitial Cajal cell hyperplasia has never been described in germline PDGFRA-mutant contexts. 3,9,10,15 Thus, the common statement that GISTs derive from interstitial Cajal cells may not be valid for PDGFRA-mutant GISTs or, in the histogenesis of this GIST subtype, there may be an early stage that passes through a cell-type devoid of usual features of interstitial Cajal cells detectable by histology and immunohistochemistry.…”

“…[5][6][7][8] More recently, CD34 + fibrous tumors of uncertain classification (henceforth simply referred to as 'fibrous tumors') have been reported in a germline PDGFRA-mutated context, constituting another possible PDGFRAmutant tumor. 9 Although GISTs and inflammatory fibroid polyps can sometimes be multiple and/or syndromic, [9][10][11][12][13][14] germline PDGFRA mutations have rarely been described, with only two familial examples. 3,9,10,15 We had the opportunity of studying a kindred presenting heterogeneous gastrointestinal mesenchymal tumors bearing an unreported inherited PDGFRA mutation.…”

“…9 Although GISTs and inflammatory fibroid polyps can sometimes be multiple and/or syndromic, [9][10][11][12][13][14] germline PDGFRA mutations have rarely been described, with only two familial examples. 3,9,10,15 We had the opportunity of studying a kindred presenting heterogeneous gastrointestinal mesenchymal tumors bearing an unreported inherited PDGFRA mutation. This unusual scenario gave us the opportunity to attempt to fully characterize the disease formerly defined as INF/NF3b and establish adequate diagnostic criteria and management strategies.…”

Gastrointestinal stromal tumors: what do we know now?

“…26,27 These mice also develop GIST-like tumors. Diffuse ICC hyperplasia has been described in several kindreds with heritable mutations in KIT (Table 2), and is associated with dysphagia and the development of multiple GISTs, 26,29,53,[73][74][75][76][77][78] although many of the tumors do not follow a malignant course.…”