80,81 Some GISTs in children (6�C14 years) and young adults (15�C24 years) occur in connection with Carney’s triad or neurofibromatosis type 1.82,83,84 Rare cases of familial GISTs are described, which carry a kit or pdgfra germline mutation.57,85,86,87,88,89,90,91,92,93 VX-770 Sporadic paediatric GISTs Two series of paediatric GISTs 6,72 showed that these tumours occur without mutations in both kit and pdgfra. They show mainly an indolent course, with treatable recurrence. A specific gene expression signature was found in five cases, including overexpression of phosphate kinase alpha 1 (PHKA1), previously reported in a subset of acute myelogenous leukaemia in elderly women.72 Paediatric GISTs associated with syndromes GISTs associated with neurofibromatosis type 1 do not have mutations in the kit or pdgfra gene, except in rare cases, not corresponding to the hot spots of sporadic GISTs.

82,94,95,96 They show an indolent course, preferential location in the small bowel and the colon and a tendency for multiple tumours.82,94,95,96 Carney’s triad97 is an association of GIST, paraganglioma and pulmonary chordoma. The genetic basis is unknown. In all, 85% of patients are women. The diagnosis is generally made at a young age or in infancy. GISTs associated with Carney’s triad do not harbour mutations in the kit or pdgfra genes.18,98 Familial GISTs are rare.57,85,86,87,88,89,90,91,92,93 Most affected families carry a kit germline mutation, inherited as autosomal dominant. One family showed a mutation is the pdgfra gene. Tumours are usually multiple and multifocal and arise at earlier ages than sporadic GISTs.

They are associated with urticaria pigmentosa, melanocytic nevi, melanomas, achalasia or neuronal hyperplasia of the myenteric plexus.57,85,86,87,88,89,90,91,92,93 Genetic mechanisms of progression are similar in familial and sporadic GISTs in adults.93 Cytogenetic changes in GISTs The cytogenetic changes in GISTs were extensively studied by using different techniques (table 44).99,100,101,102,103,104,105,106,107,108 Table 4Summary of cytogenetic changes in gastrointestinal stromal tumours A correlation between the number and type of chromosomal changes and biological behaviour of GISTs was suggested.21 Karyotypes from about 60% of GISTs show a partial or total loss of chromosome 14.21,45,104,109 In particular, 14q11.

1�C12 and 14q22�C24 are frequently deleted and can therefore represent sites for tumour suppressor genes participating early in the genesis of GISTs.104,110 Dacomitinib Loss of 22q is observed in about half of GISTs, with a higher frequency in advanced tumours.77,111 It is possible therefore that an unknown gene on 22q may be responsible in the early stages of tumorigenesis and in tumour progression.18,45,111 Intermediate�\risk and high�\risk GISTs show loss of chromosomes 1p, 9p, 9q, 11p100,102,104,106,108,111 and gains of 8q and 17q.