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

Human Pathology
Karen E MatsukumaIris Schrijver

Abstract

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.

References

Jun 5, 2007·JAMA : the Journal of the American Medical Association·Pardeep KaurahDavid Huntsman
Apr 9, 2008·The American Journal of Surgical Pathology·William M RogersTeri A Longacre
Sep 13, 2008·The Journal of Pathology·M BarberR C Fitzgerald
Jan 27, 2009·Human Molecular Genetics·Carla OliveiraDavid Huntsman
Feb 19, 2009·Cancer Research·Bostjan HumarParry Guilford

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Citations

Jun 23, 2012·Clinical Medicine & Research·Adedayo A OnitiloJessica M Engel
Jul 16, 2015·Arquivos Brasileiros De Cirurgia Digestiva : ABCD = Brazilian Archives of Digestive Surgery·Eurico Cleto Ribeiro de CamposTeresa Cristina Santos Cavalcanti
Nov 19, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Qiu PengQianjin Liao

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