The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA.
Umut DiselRussell MadisonKumar AbhishekJon H ChungSally E TrabuccoAsli O MatosGarrett M FramptonLee A AlbackerVenkataprasanth ReddyNuri KaradurmusAdam BensonJennifer WebsterSemra PaydasRuben CabanillasChaitali NangiaM A OzturkSherri Z MillisSumanta K PalBreelyn WilkyEthan S SokolLaurie M GaySalil SomanShridar GanesanKatherine JanewayPhil J StephensViola W ZhuSai-Hong Ignatius OuChristine M LovlyMrinal GounderAlexa B SchrockJeffrey S RossVincent A MillerSamuel J KlempnerSiraj M AliPublished in: The oncologist (2019)
Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.