Hereditary diffuse gastric cancer due to a previously undescribed CDH1 splice site mutation

Karen Matsukuma, Franklin M. Mullins, Lisa Dietz, James L. Zehnder, James M. Ford, Nicolette M. Chun, Iris Schrijver

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Our patient was a 52-year-old man who was diagnosed with signet ring cell gastric adenocarcinoma. An extensive family history of gastric cancer raised suspicion for hereditary diffuse gastric cancer. Sequencing of the patient's CDH1 gene revealed a novel point mutation in a strictly conserved splice site within intron 6, c.833-2 A > G. This mutation was predicted to result in loss of function due to defective RNA splicing. To characterize the pathogenic mechanism of this mutation, we amplified the patient's CDH1 gene products by reverse transcriptase polymerase chain reaction. Primers flanking the region of the mutation detected 3 distinct transcripts. In addition to the wild-type product, a larger product consistent with activation of a cryptic splice site within intron 6 and a smaller product shown to result from exon 7 skipping were detected. In summary, we have identified a novel CDH1 mutation in a large hereditary diffuse gastric cancer kindred and identified its pathogenic mechanism.

Original languageEnglish (US)
Pages (from-to)1200-1203
Number of pages4
JournalHuman Pathology
Issue number8
StatePublished - Aug 1 2010
Externally publishedYes


  • CDH1
  • Gastric cancer
  • HDGC
  • Mutation
  • Splicing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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