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Familial Cancer

, Volume 6, Issue 1, pp 147–152 | Cite as

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

  • W. Stewart
  • J. P. Traynor
  • A. Cooke
  • S. Griffiths
  • N. F. Őnen
  • M. Balsitis
  • A. A. Shah
  • M. Upadhyaya
  • E. S. Tobias
Brief communication

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.

Keywords

Neurofibromatosis NF1 Gastric carcinoid LOH 

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

Notes

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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Copyright information

© Springer Science + Business Media B.V. 2006

Authors and Affiliations

  • W. Stewart
    • 1
  • J. P. Traynor
    • 2
  • A. Cooke
    • 3
  • S. Griffiths
    • 4
  • N. F. Őnen
    • 2
  • M. Balsitis
    • 1
  • A. A. Shah
    • 2
  • M. Upadhyaya
    • 4
  • E. S. Tobias
    • 3
  1. 1.Department of PathologyCrosshouse HospitalKilmarnockUK
  2. 2.Department of GastroenterologyCrosshouse HospitalKilmarnockUK
  3. 3.Duncan Guthrie Institute of Medical GeneticsYorkhill HospitalsGlasgowUK
  4. 4.Institute of Medical Genetics University of Wales College of MedicineCardiffUK

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