Journal of Gastroenterology

, Volume 41, Issue 4, pp 378–382

Novel NF1 gene mutation in a Japanese patient with neurofibromatosis type 1 and a gastrointestinal stromal tumor

  • Hiroshi Nemoto
  • Genshu Tate
  • Annalisa Schirinzi
  • Takao Suzuki
  • Shoji Sasaya
  • Yasuo Yoshizawa
  • Takemasa Midorikawa
  • Toshiyuki Mitsuya
  • Bruno Dallapiccola
  • Yutaka Sanada
Case report


Many mutations of the NF1 gene have been reported in patients with neurofibromatosis type 1 (NF1); however, there have been no documented NF1 gene mutations in Japanese NF1 patients. In the present study, we used the polymerase chain reaction (PCR) and DNA sequencing analysis to characterize the NF1 gene in a 53-year-old Japanese patient with NF1 who suffered from neurofibroma, pheochromocytoma, and gastrointestinal stromal tumor (GIST). Direct sequence analyses revealed a single base substitution in the splicing donor site of intron 6 (IVS6 888+1, G → A) in one NF1 allele, resulting in an altered splice site (ss) in the mutated allele. Splicing at the cryptic 5′ ss in the mutated allele generated mRNA with an insertion of 60 nucleotides. In addition, we screened for mutations in exons 9, 11, 13, and 17 of the c-kit gene in GIST and the succinate dehydrogenase subunit D (SDHD) gene in the pheochromocytoma, but we did not detect any somatic mutations. We report here the first case of an NF1 patient with four neoplasms: neurofibroma, pheochromocytoma, astrocytoma and GIST. Our results suggest that the molecular pathogenesis of GISTs in NF1 patients is different from that in non-NF1 patients.

Key words

neurofibromatosis type 1 gastrointestinal stromal tumor pheochromocytoma NF1 c-kit CD117 succinate dehydrogenase D 


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Copyright information

© Springer-Verlag Tokyo 2006

Authors and Affiliations

  • Hiroshi Nemoto
    • 1
  • Genshu Tate
    • 2
  • Annalisa Schirinzi
    • 3
  • Takao Suzuki
    • 2
  • Shoji Sasaya
    • 1
  • Yasuo Yoshizawa
    • 1
  • Takemasa Midorikawa
    • 1
  • Toshiyuki Mitsuya
    • 2
  • Bruno Dallapiccola
    • 3
  • Yutaka Sanada
    • 1
  1. 1.Department of SurgeryShowa University Fujigaoka HospitalYokohamaJapan
  2. 2.Department of Surgical PathologyShowa University Fujigaoka HospitalYokohamaJapan
  3. 3.IRCCS-CSS, San Giovanni Rotondo and CSS-Mendel Institute, Department of Experimental Medicine and PathologyUniversity of Rome “La Sapienza”RomeItaly

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