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Gastric carcinoid: germline and somatic mutation of the neurofibromatosis type 1 gene

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Abstract

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominantly inherited conditions. A range of complications has been described, including gastrointestinal manifestations. Gastric carcinoid tumours are associated with multiple endocrine neoplasia, atrophic gastritis and pernicious anaemia but have not been reported in NF1 in the absence of other predisposing factors. We report the occurrence and investigation of a gastric carcinoid tumour in a 23-year-old woman with previously uncomplicated NF1. Analysis of the tumour tissue revealed loss of heterozygosity at the NF1 gene locus but a normal karyotype and an absence of microsatellite instability. A germline NF1 gene nonsense mutation in exon 37 was detected by denaturing high-performance liquid chromatography and DNA sequence analysis. This is the first reported occurrence of a gastric carcinoid tumour in a patient with NF1 in the absence of other predisposing factors such as pernicious anaemia. The analyses indicate that the carcinoid arose through NF1 gene inactivation but in the absence of an inherited NF1 gene microdeletion. This case adds to the range of gastrointestinal tumours that may be encountered in patients with NF1, particularly in those who present with upper gastrointestinal haemorrhage.

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Abbreviations

dHPLC:

Denaturing high-performance liquid chromatography

GAP:

GTPase activating protein

GDB:

Human genome database

GDP:

Guanosine 5′-diphosphate

GIST:

Gastrointestinal stromal tumour

GRD:

GAP-related domain

GTP:

Guanosine 5′-triphosphate

LOH:

Loss of heterozygosity

MSI:

Microsatellite instability

MPNST:

Malignant peripheral nerve sheath tumour

NCAM:

Neural cell adhesion molecule

NF1:

Neurofibromatosis type 1

PCR:

Polymerase chain reaction

PGP 9.5:

Protein gene product 9.5

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Acknowledgements

We are very grateful to Dr. Susan Huson for her helpful advice and discussion regarding this case. The corresponding author is a recipient of a GlaxoSmithKline senior clinical research fellowship.

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Authors and Affiliations

  1. Department of Pathology, Crosshouse Hospital, Kilmarnock, KA2 0BE, UK

    W. Stewart & M. Balsitis

  2. Department of Gastroenterology, Crosshouse Hospital, Kilmarnock, KA2 0BE, UK

    J. P. Traynor, N. F. Őnen & A. A. Shah

  3. Duncan Guthrie Institute of Medical Genetics, Yorkhill Hospitals, NHS Greater Glasgow, Dalnair Street, Glasgow, G3 8SJ, UK

    A. Cooke & E. S. Tobias

  4. Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK

    S. Griffiths & M. Upadhyaya

Authors
  1. W. Stewart
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  2. J. P. Traynor
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  3. A. Cooke
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  4. S. Griffiths
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  5. N. F. Őnen
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  6. M. Balsitis
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  7. A. A. Shah
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  8. M. Upadhyaya
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  9. E. S. Tobias
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Corresponding author

Correspondence to E. S. Tobias.

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Stewart, W., Traynor, J.P., Cooke, A. et al. Gastric carcinoid: germline and somatic mutation of the neurofibromatosis type 1 gene. Familial Cancer 6, 147–152 (2007). https://doi.org/10.1007/s10689-006-9002-2

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  • DOI: https://doi.org/10.1007/s10689-006-9002-2

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