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Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor.

Bosbach B, Rossi F, Yozgat Y, Loo J, Zhang JQ, Berrozpe G, Warpinski K, Ehlers I, Veach D, Kwok A, Manova K, Antonescu CR, DeMatteo RP, Besmer P.

Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8448-E8457. doi: 10.1073/pnas.1711449114. Epub 2017 Sep 18.


Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor.

Zeng S, Seifert AM, Zhang JQ, Cavnar MJ, Kim TS, Balachandran VP, Santamaria-Barria JA, Cohen NA, Beckman MJ, Medina BD, Rossi F, Crawley MH, Loo JK, Maltbaek JH, Besmer P, Antonescu CR, DeMatteo RP.

Mol Cancer Ther. 2017 Sep;16(9):1954-1966. doi: 10.1158/1535-7163.MCT-17-0139. Epub 2017 Jun 13.


PD-1/PD-L1 Blockade Enhances T-cell Activity and Antitumor Efficacy of Imatinib in Gastrointestinal Stromal Tumors.

Seifert AM, Zeng S, Zhang JQ, Kim TS, Cohen NA, Beckman MJ, Medina BD, Maltbaek JH, Loo JK, Crawley MH, Rossi F, Besmer P, Antonescu CR, DeMatteo RP.

Clin Cancer Res. 2017 Jan 15;23(2):454-465. doi: 10.1158/1078-0432.CCR-16-1163. Epub 2016 Jul 28.


A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.

Buono M, Facchini R, Matsuoka S, Thongjuea S, Waithe D, Luis TC, Giustacchini A, Besmer P, Mead AJ, Jacobsen SE, Nerlov C.

Nat Cell Biol. 2016 Feb;18(2):157-67. doi: 10.1038/ncb3299. Epub 2016 Jan 18.


Pharmacological Inhibition of KIT Activates MET Signaling in Gastrointestinal Stromal Tumors.

Cohen NA, Zeng S, Seifert AM, Kim TS, Sorenson EC, Greer JB, Beckman MJ, Santamaria-Barria JA, Crawley MH, Green BL, Rossi F, Besmer P, Antonescu CR, DeMatteo RP.

Cancer Res. 2015 May 15;75(10):2061-70. doi: 10.1158/0008-5472.CAN-14-2564. Epub 2015 Apr 2.


Combined inhibition of MAP kinase and KIT signaling synergistically destabilizes ETV1 and suppresses GIST tumor growth.

Ran L, Sirota I, Cao Z, Murphy D, Chen Y, Shukla S, Xie Y, Kaufmann MC, Gao D, Zhu S, Rossi F, Wongvipat J, Taguchi T, Tap WD, Mellinghoff IK, Besmer P, Antonescu CR, Chen Y, Chi P.

Cancer Discov. 2015 Mar;5(3):304-15. doi: 10.1158/2159-8290.CD-14-0985. Epub 2015 Jan 8.


Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor.

Kim TS, Cavnar MJ, Cohen NA, Sorenson EC, Greer JB, Seifert AM, Crawley MH, Green BL, Popow R, Pillarsetty N, Veach DR, Ku AT, Rossi F, Besmer P, Antonescu CR, Zeng S, Dematteo RP.

Clin Cancer Res. 2014 May 1;20(9):2350-62. doi: 10.1158/1078-0432.CCR-13-3033. Epub 2014 Feb 28.


KIT oncogene inhibition drives intratumoral macrophage M2 polarization.

Cavnar MJ, Zeng S, Kim TS, Sorenson EC, Ocuin LM, Balachandran VP, Seifert AM, Greer JB, Popow R, Crawley MH, Cohen NA, Green BL, Rossi F, Besmer P, Antonescu CR, DeMatteo RP.

J Exp Med. 2013 Dec 16;210(13):2873-86. doi: 10.1084/jem.20130875. Epub 2013 Dec 9.


KIT receptor gain-of-function in hematopoiesis enhances stem cell self-renewal and promotes progenitor cell expansion.

Deshpande S, Bosbach B, Yozgat Y, Park CY, Moore MA, Besmer P.

Stem Cells. 2013 Aug;31(8):1683-95. doi: 10.1002/stem.1419.


SDHA loss of function mutations in a subset of young adult wild-type gastrointestinal stromal tumors.

Italiano A, Chen CL, Sung YS, Singer S, DeMatteo RP, LaQuaglia MP, Besmer P, Socci N, Antonescu CR.

BMC Cancer. 2012 Sep 14;12:408. doi: 10.1186/1471-2407-12-408.


Imatinib resistance and microcytic erythrocytosis in a KitV558Δ;T669I/+ gatekeeper-mutant mouse model of gastrointestinal stromal tumor.

Bosbach B, Deshpande S, Rossi F, Shieh JH, Sommer G, de Stanchina E, Veach DR, Scandura JM, Manova-Todorova K, Moore MA, Antonescu CR, Besmer P.

Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):E2276-83. doi: 10.1073/pnas.1115240109. Epub 2012 May 31.


The expression of the glucocorticoid receptor in human erythroblasts is uniquely regulated by KIT ligand: implications for stress erythropoiesis.

Varricchio L, Tirelli V, Masselli E, Ghinassi B, Saha N, Besmer P, Migliaccio AR.

Stem Cells Dev. 2012 Oct 10;21(15):2852-65. doi: 10.1089/scd.2011.0676. Epub 2012 Jul 9.


CD133 and CD44 are universally overexpressed in GIST and do not represent cancer stem cell markers.

Chen J, Guo T, Zhang L, Qin LX, Singer S, Maki RG, Taguchi T, Dematteo R, Besmer P, Antonescu CR.

Genes Chromosomes Cancer. 2012 Feb;51(2):186-95. doi: 10.1002/gcc.20942. Epub 2011 Nov 10.


Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido.

Balachandran VP, Cavnar MJ, Zeng S, Bamboat ZM, Ocuin LM, Obaid H, Sorenson EC, Popow R, Ariyan C, Rossi F, Besmer P, Guo T, Antonescu CR, Taguchi T, Yuan J, Wolchok JD, Allison JP, DeMatteo RP.

Nat Med. 2011 Aug 28;17(9):1094-100. doi: 10.1038/nm.2438.


Visualization of the interstitial cells of cajal (ICC) network in mice.

Chen Y, Shamu T, Chen H, Besmer P, Sawyers CL, Chi P.

J Vis Exp. 2011 Jul 27;(53). pii: 2802. doi: 10.3791/2802.


Imatinib upregulates compensatory integrin signaling in a mouse model of gastrointestinal stromal tumor and is more effective when combined with dasatinib.

Rossi F, Yozgat Y, de Stanchina E, Veach D, Clarkson B, Manova K, Giancotti FG, Antonescu CR, Besmer P.

Mol Cancer Res. 2010 Sep;8(9):1271-83. doi: 10.1158/1541-7786.MCR-10-0065. Epub 2010 Aug 24.


Kit ligand cytoplasmic domain is essential for basolateral sorting in vivo and has roles in spermatogenesis and hematopoiesis.

Deshpande S, Agosti V, Manova K, Moore MA, Hardy MP, Besmer P.

Dev Biol. 2010 Jan 15;337(2):199-210. doi: 10.1016/j.ydbio.2009.10.022. Epub 2009 Oct 27.


Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance.

Guo T, Hajdu M, Agaram NP, Shinoda H, Veach D, Clarkson BD, Maki RG, Singer S, Dematteo RP, Besmer P, Antonescu CR.

Clin Cancer Res. 2009 Nov 15;15(22):6862-70. doi: 10.1158/1078-0432.CCR-09-1315. Epub 2009 Oct 27.


Kit signaling via PI3K promotes ovarian follicle maturation but is dispensable for primordial follicle activation.

John GB, Shidler MJ, Besmer P, Castrillon DH.

Dev Biol. 2009 Jul 15;331(2):292-9. doi: 10.1016/j.ydbio.2009.05.546. Epub 2009 May 15.


A KIT juxtamembrane PY567 -directed pathway provides nonredundant signals for erythroid progenitor cell development and stress erythropoiesis.

Agosti V, Karur V, Sathyanarayana P, Besmer P, Wojchowski DM.

Exp Hematol. 2009 Feb;37(2):159-71. doi: 10.1016/j.exphem.2008.10.009. Epub 2008 Dec 18.


Changes in the structure and function of ICC networks in ICC hyperplasia and gastrointestinal stromal tumors.

Kwon JG, Hwang SJ, Hennig GW, Bayguinov Y, McCann C, Chen H, Rossi F, Besmer P, Sanders KM, Ward SM.

Gastroenterology. 2009 Feb;136(2):630-9. doi: 10.1053/j.gastro.2008.10.031. Epub 2008 Nov 1.


Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors.

Agaram NP, Wong GC, Guo T, Maki RG, Singer S, Dematteo RP, Besmer P, Antonescu CR.

Genes Chromosomes Cancer. 2008 Oct;47(10):853-9. doi: 10.1002/gcc.20589.


Molecular characterization of pediatric gastrointestinal stromal tumors.

Agaram NP, Laquaglia MP, Ustun B, Guo T, Wong GC, Socci ND, Maki RG, DeMatteo RP, Besmer P, Antonescu CR.

Clin Cancer Res. 2008 May 15;14(10):3204-15. doi: 10.1158/1078-0432.CCR-07-1984.


Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST).

Dematteo RP, Gold JS, Saran L, Gönen M, Liau KH, Maki RG, Singer S, Besmer P, Brennan MF, Antonescu CR.

Cancer. 2008 Feb 1;112(3):608-15.


Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor.

Guo T, Agaram NP, Wong GC, Hom G, D'Adamo D, Maki RG, Schwartz GK, Veach D, Clarkson BD, Singer S, DeMatteo RP, Besmer P, Antonescu CR.

Clin Cancer Res. 2007 Aug 15;13(16):4874-81.


L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.

Antonescu CR, Busam KJ, Francone TD, Wong GC, Guo T, Agaram NP, Besmer P, Jungbluth A, Gimbel M, Chen CT, Veach D, Clarkson BD, Paty PB, Weiser MR.

Int J Cancer. 2007 Jul 15;121(2):257-64.


Histone H2AX is a mediator of gastrointestinal stromal tumor cell apoptosis following treatment with imatinib mesylate.

Liu Y, Tseng M, Perdreau SA, Rossi F, Antonescu C, Besmer P, Fletcher JA, Duensing S, Duensing A.

Cancer Res. 2007 Mar 15;67(6):2685-92.


Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19.

Kawaguchi N, Horiuchi K, Becherer JD, Toyama Y, Besmer P, Blobel CP.

J Cell Sci. 2007 Mar 15;120(Pt 6):943-52.


Pathologic and molecular heterogeneity in imatinib-stable or imatinib-responsive gastrointestinal stromal tumors.

Agaram NP, Besmer P, Wong GC, Guo T, Socci ND, Maki RG, DeSantis D, Brennan MF, Singer S, DeMatteo RP, Antonescu CR.

Clin Cancer Res. 2007 Jan 1;13(1):170-81.


Comparative ultrastructural analysis and KIT/PDGFRA genotype in 125 gastrointestinal stromal tumors.

Agaram NP, Baren A, Arkun K, Dematteo RP, Besmer P, Antonescu CR.

Ultrastruct Pathol. 2006 Nov-Dec;30(6):443-52.


Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor.

Rossi F, Ehlers I, Agosti V, Socci ND, Viale A, Sommer G, Yozgat Y, Manova K, Antonescu CR, Besmer P.

Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12843-8. Epub 2006 Aug 14.


The scaffolding adapter Gab2, via Shp-2, regulates kit-evoked mast cell proliferation by activating the Rac/JNK pathway.

Yu M, Luo J, Yang W, Wang Y, Mizuki M, Kanakura Y, Besmer P, Neel BG, Gu H.

J Biol Chem. 2006 Sep 29;281(39):28615-26. Epub 2006 Jul 27.


A distant upstream locus control region is critical for expression of the Kit receptor gene in mast cells.

Berrozpe G, Agosti V, Tucker C, Blanpain C, Manova K, Besmer P.

Mol Cell Biol. 2006 Aug;26(15):5850-60.


Lyn kinase promotes erythroblast expansion and late-stage development.

Karur VG, Lowell CA, Besmer P, Agosti V, Wojchowski DM.

Blood. 2006 Sep 1;108(5):1524-32. Epub 2006 May 16.


Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate.

Cammenga J, Horn S, Bergholz U, Sommer G, Besmer P, Fiedler W, Stocking C.

Blood. 2005 Dec 1;106(12):3958-61. Epub 2005 Aug 4.


Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation.

Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG, DeMatteo RP.

Clin Cancer Res. 2005 Jun 1;11(11):4182-90.


Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature.

Prakash S, Sarran L, Socci N, DeMatteo RP, Eisenstat J, Greco AM, Maki RG, Wexler LH, LaQuaglia MP, Besmer P, Antonescu CR.

J Pediatr Hematol Oncol. 2005 Apr;27(4):179-87. Review.


Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study.

Yantiss RK, Rosenberg AE, Sarran L, Besmer P, Antonescu CR.

Mod Pathol. 2005 Apr;18(4):475-84.


Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site.

Antonescu CR, Viale A, Sarran L, Tschernyavsky SJ, Gonen M, Segal NH, Maki RG, Socci ND, DeMatteo RP, Besmer P.

Clin Cancer Res. 2004 May 15;10(10):3282-90.


Critical role for Kit-mediated Src kinase but not PI 3-kinase signaling in pro T and pro B cell development.

Agosti V, Corbacioglu S, Ehlers I, Waskow C, Sommer G, Berrozpe G, Kissel H, Tucker CM, Manova K, Moore MA, Rodewald HR, Besmer P.

J Exp Med. 2004 Mar 15;199(6):867-78.


Pleomorphic characteristics of a germ-line KIT mutation in a large kindred with gastrointestinal stromal tumors, hyperpigmentation, and dysphagia.

Robson ME, Glogowski E, Sommer G, Antonescu CR, Nafa K, Maki RG, Ellis N, Besmer P, Brennan M, Offit K.

Clin Cancer Res. 2004 Feb 15;10(4):1250-4.


Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors.

Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, Robson M, Maki R, Brennan MF, Ladanyi M, DeMatteo RP, Besmer P.

Clin Cancer Res. 2003 Aug 15;9(9):3329-37.


A role for kit receptor signaling in Leydig cell steroidogenesis.

Rothschild G, Sottas CM, Kissel H, Agosti V, Manova K, Hardy MP, Besmer P.

Biol Reprod. 2003 Sep;69(3):925-32. Epub 2003 May 28.


Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase.

Sommer G, Agosti V, Ehlers I, Rossi F, Corbacioglu S, Farkas J, Moore M, Manova K, Antonescu CR, Besmer P.

Proc Natl Acad Sci U S A. 2003 May 27;100(11):6706-11. Epub 2003 May 16.


Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand.

Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S.

Cell. 2002 May 31;109(5):625-37.


Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses.

Kissel H, Timokhina I, Hardy MP, Rothschild G, Tajima Y, Soares V, Angeles M, Whitlow SR, Manova K, Besmer P.

EMBO J. 2000 Mar 15;19(6):1312-26.


The W(sh), W(57), and Ph Kit expression mutations define tissue-specific control elements located between -23 and -154 kb upstream of Kit.

Berrozpe G, Timokhina I, Yukl S, Tajima Y, Ono M, Zelenetz AD, Besmer P.

Blood. 1999 Oct 15;94(8):2658-66.


Consequences of exclusive expression in vivo of Kit-ligand lacking the major proteolytic cleavage site.

Tajima Y, Moore MA, Soares V, Ono M, Kissel H, Besmer P.

Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11903-8.

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