Genetic aberrations of gastrointestinal stromal tumors

Yang, Jilong; Du, Xiaoling; Lazar, Alexander J.; Pollock, Raphael E.; Hunt, Kelly K.; Chen, Kexin; Hao, Xishan; Trent, Jonathan C.; Zhang, Wei

doi:10.1002/cncr.23778

Cited by 69 publications

(58 citation statements)

References 69 publications

(61 reference statements)

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“…The significance of these changes has not been thoroughly investigated. 7 A comprehensive and integrative analysis of gene expression profiling and highresolution genomic copy number could improve our understanding of GIST tumor development and progression. Here, we report the first study integrating gene expression profiling and high-resolution genomic copy number analyses in GISTs.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] In addition to KIT and PDGFRA mutations, sequential accumulation of other genetic events may be involved in the development and progression of GIST. 7 Loss of chromosomes 14 and 22 is the most frequently described genetic aberration in GISTs, regardless of tumor genotype. These chromosomal losses may represent an underlying pathogenetic event resulting in the inactivation or haploinsufficiency of tumor suppressor genes.…”

mentioning

confidence: 99%

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A molecular portrait of gastrointestinal stromal tumors: an integrative analysis of gene expression profiling and high-resolution genomic copy number

Astolfi

Nannini

Pantaleo

et al. 2010

Laboratory Investigation

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In addition to KIT and PDGFRA mutations, sequential accumulation of other genetic events is involved in the development and progression of gastrointestinal stromal tumors (GISTs). Until recently, the significance of these other alterations has not been thoroughly investigated. We report the first study that integrates gene expression profiling and high-resolution genomic copy number analyses in GIST. Fresh tissue specimens from 25 patients with GIST were collected, and gene expression profiling and high-resolution genomic copy number analyses were performed, using Affymetrix U133Plus and SNP array 6.0. We found that all 21 mutant GIST patients showed both macroscopic cytogenetic alterations and cryptic microdeletions or amplifications, whereas 75% (three of four) of wild-type patients with GIST did not show genomic imbalances. The most frequently observed chromosomal alterations in patients with mutant GIST included 14q complete or partial deletion (17 of 25), 1p deletion (14 of 25) and 22q deletion (10 of 25). Genetic targets of the chromosomal aberrations were selected by integrated analysis of copy number and gene expression data. We detected the involvement of known oncogenes and tumor suppressors including KRAS in chr 12p amplification and KIF1B, PPM1A, NF2 in chr 1p, 14q and 22p deletions, respectively. The genomic segment most frequently altered in mutated samples was the 14q23.1 region, which contains potentially novel tumor suppressors, including DAAM1, RTN1 and DACT1. siRNA-mediated RTN1 downregulation showed evidence for the potential role in GIST pathogenesis. The combination of gene expression profiling and high-resolution genomic copy number analysis offers a detailed molecular portrait of GISTs, providing an essential comprehensive knowledge necessary to guide the discovery of novel target genes involved in tumor development and progression.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A molecular portrait of gastrointestinal stromal tumors: an integrative analysis of gene expression profiling and high-resolution genomic copy number

Astolfi

Nannini

Pantaleo

et al. 2010

Laboratory Investigation

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“…G‹ST'ler, gastrointestinal sistemde (ya da nadiren di¤er abdominal veya retroperitoneal bölgelerde) yer alan mezenkimal/stromal hücrelerden kaynaklanan tümörlerdir (1,3). Ortalama görülme yafl› 55-60't›r.…”

Section: Tartifimaunclassified

İnce barsak gastrointestinal stromal tümörü (GİST): Olgu sunumu

Güler¹,

Sezer²,

Erol³

et al. 2015

Endoskopi Gastrointestinal

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G‹R‹fiGastrointestinal stromal tümörler (GIST), sindirim sisteminden (mide, ince barsak, mezenter, kolon, özofagus) kaynaklanan submukozal tümörlerdir. GIST'ler en s›k midede (%50-%70), ikinci s›kl›kta ince barsakta (%20-%30) ve kal›n barsakta ortaya ç›karlar (yaklafl›k %10) (1,2). Daha nadir olarak omentum ve mezenter gibi baflka bölgelerde lokalize olabilirler. Tipik olarak %90'dan fazlas›nda spesifik bir K‹T veya PDGFRA gen mutasyonu mevcuttur (3). Bu olgu sunumunda kanl› d›flk›lama flikayeti ile baflvuran bir hastada saptanan ince barsak gastrointestinal stromal tümörünün tan› ve tedavisini irdelemeyi amaçlad›k. OLGU SUNUMU30 yafl›nda erkek hasta; yaklafl›k 3 y›ld›r devam eden, yemeklerden sonra artan kar›n a¤r›s› ve ara ara olan kanl› d›flk›lama flikayeti ile gastroenteroloji klini¤ine baflvurdu, mevcut bulgular eflli¤inde ileri tetkik ve tedavi amac›yla klini¤imize refere edildi.Hastan›n fizik muayenesinde kar›n orta kadranda yaklafl›k 15 cm büyüklü¤ünde immobil kitle mevcut idi. Mevcut bulgular eflli¤inde hastan›n çekilen bat›n bilgisayarl› tomografisi (BT); 'bat›nda orta hatt›n solunda aksiyel planda en genifl yerinde 12x9,5 cm boyutunda ölçülen santrali kistik natürde büyük boyutlu lezyon izlenmifl olup, öncelikle jejunal kökenli G‹ST'e ait olabilece¤i düflünülmüfltür, uzak organ metastaz›-na ait olabilecek bulgu saptanmam›flt›r' fleklinde rapor edildi. Bunun üzerine çekilen bat›n manyetik rezonans enterografisi; 'bat›n sol yar›s›nda jejenum kökenli oldu¤u düflünülen gross kitle lezyonu gözlenmifltir, radyolojik bulgular G‹ST olas›l›¤›-n› ön planda düflündürmüfltür, invazyon ya da metastaz bulgusu kesit alan›na giren yap›lar dahilinde izlenmemifltir' fleklinde rapor edildi.Hastaya ince barsak gastrointestinal stromal tümörü ön tan›-s›yla parsiyel ince barsak rezeksiyonu ve yan yana barsak anastomozu uyguland› (Resim 1). Postoperatif dönemde barsak pasaj› aç›k olan ve oral al›m› tolere eden hasta, ek cerrahi komplikasyon geliflmemesi üzerine salah ile taburcu edildi.Hastan›n patoloji sonucu; 'gastrointesstinal stromal tümör, en büyük çap› 11,5 cm olan tümörde 50 büyük büyütme alan›n-da 3 mitoz izlenmifl olup, tümör ince barsak duvar›nda kas dokular› içerisinde yerleflmifl ekspansif büyüyerek submukozaya uzanm›flt›r, mukozal tutulum, ülserasyon izlenmemifltir, cerrahi s›n›rlar tümörsüzdür' fleklinde rapor edildi. TARTIfiMAG‹ST'ler, gastrointestinal sistemde (ya da nadiren di¤er abdominal veya retroperitoneal bölgelerde) yer alan mezenkimal/stromal hücrelerden kaynaklanan tümörlerdir (1,3). Ortalama görülme yafl› 55-60't›r. Görülme oran› K=E (4,5). En Gastrointestinal stromal tümörler, sindirim sisteminden (mide, ince barsak, mezenter, kolon, özofagus) kaynaklanan submukozal tümörlerdir. Gastrointestinal stromal tümörler en s›k midede (%50-%70), ikinci s›kl›kta ince barsakta (%20-%30) ve kal›n barsakta ortaya ç›karlar (yaklafl›k %10). Yaklafl›k %50 oran›nda tan› kondu¤unda metastaz yapm›fl durumdad›r ve en s›k karaci¤er ve peritona metastaz yapar. Cerrahi, gastrointestinal stromal tümörler tan›s›n› histolo...

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“…Дополнительно в па-тогенез ГИСО вовлечены другие гены [36]. Хромосом-ные аберрации включают утрату 1p, 13q, 14q или 15q, потерю гетерозиготности на 22q, многочисленные аллельные и микросателлитные нарушения.…”

unclassified

“…В 10 % ГИСО наблюдается гомозиготная делеция гена Hox11L1, который локализован на хромосоме 2 и иг-рает роль в пролиферации интерстициальных клеток Кахаля [43]. Амплификация генов C-MYC, MDM2, EGFR1 и CCND1 и высокая экспрессия матричная РНМ (мPHK) генов CDK4, RB1, MDM2, TP53 и E2F1 коррелирует с агрессивным поведением и неблагопри-ятным прогнозом ГИСО [36]. В частности, высокая экспрессия E2F1 ассоциирована с количеством мито-зов, скоростью пролиферации, мутациями KIT и аг-рессивным поведением опухоли [36,44].…”

unclassified