Etiology

 sporadic GISTs

• gain-of-function mutations of c-kit receptor tyrosine kinase (KIT) gene
• gain-of-function mutations of PDGFR-alpha gene coding for platelet-derived growth factor receptor (PDGFRA) alpha (#12949711#)

 NF-associated GISTs

• NF germline mutations
• no KIT or PDGFRA mutations (#16096406#)

Predisposition

 neurofibromatosis type 1 (NF1) (#16096406#)
 Carney triad (#15712189#)

Differential diagnosis (#11215292#)

 digestive sarcomas

• digestive leiomyosarcoma
• digestive fibrosarcoma

Prognosis

 local recurrence
 metastasis

• ovary (#15958857#)

Cytogenetics

 ploidy anomalies

• hypo- to near-diploid
• near-triploid
• hypotetraploid

 loss of chromosome 14
 loss of 22q: 22q13, (#15580284#)
 loss of both chromosomes 14 and 22
 loss of 9p21 (54%) (p16INK4a and p14ARF gene loss) (#15929122#)
 loss of 1p
 loss of 15
 loss of 3p
 loss of 13q
 loss of 10q
 loss of 19

CGH (#14730211#, #9406576#)

Molecular biology

 KIT or PDGFRA mutations (90%)

• KIT activating mutations (70%)
• PDGFRA activating mutations (20%)

 KIT overexpression (95%)
 rare KIT amplification (#15869870#)

 allelic losses (loss of heterozygosity)

• 9p21 LOH (#15181453#)
• 14q LOH (47%-65%) (#11123422#, #10942800#)
• 22q LOH (50%-75%) (#15580284#, #11123422#, #10942800#)

 gene overpexpression and amplification (#15864317#)

• CMYC (3.3%) (#15864317#)
• MDM2 (5.3%) (#15864317#)
• EGFR1 (5.3%) (#15864317#)
• CCND1 (8.9%) (#15864317#)