A malignant gastrointestinal stromal tumour in a patient with multiple endocrine neoplasia type 1

Loss of heterozygosity for polymorphic markers flanking the multiple endocr ine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumou rs from subjects with MEN-1 has been well documented and has led to the hyp othesis that the MEN-1 gene functions as a recessive! tumour suppressor gen e, We report a case of MEN-1 with duodeno-pancreatic gastrinoma, parathyroi d hyperplasia, pituitary adenoma, adrenal adenoma, and lipomas, whose rare association with a malignant gastrointestinal stromal tumour (GIST) represe nts an undescribed combination, MEN-1 mutation in this family was shown as a frameshift (1607delA) in exon 10. To assess the role of the MEN-1 gene in the pathogenesis of tumours less commonly associated with MEN-1, we studie d GIST DNA for loss of the unaffected MEN-1 gene allele. Stromal tumour and peripheral leucocyte DNAs from our patient were examined for loss of heter ozygosity using the PYGM microsatellite polymorphism and an intragenic poly morphism (D418D in exon 9) in the MEN-1 gene. We showed no evidence for los s of the wild-type MEN-1 allele in GIST. The MEN-1 germline inactivating mu tation 1607delA-ter558 in exon 10 was detected in the stromal tumour DNA, b ut no somatic mutation in the wild-type MEN-1 allele in GIST DNA was detect ed. Occurrence of GIST could be consistent with the possibility that this M EN-1-related uncommon neoplasm arose independently by a mechanism unrelated to the MEN-1 gene. Eur J Gastroenterol Hepatol 13:207-211 (C) 2001 Lippinc ott Williams & Wilkins.