Early-onset diffuse gastric cancer associated with a de novo large genomic deletion of CDH1 gene

A 41-year-old man with no familial history of gastric cancer was diagnosed as with intramucosal early gastric cancer. Two months after the first endoscopic submucosal dissection for signet-ring cell carcinoma (SRCC), the appearance of previously unrecognized multiple erosions of SRCC was noticed. Pathological examination after a total gastrectomy and Roux-en-Y reconstruction with D2 lymph node dissection were performed. Postoperative pathological examination revealed 90 and more lesions, which tempted the attending pathologist to refer to genetic tests for the predisposition though the patient had no familial history of gastric cancer. There were no mutations in all the exons of CDH1 with conventional DNA sequencing, but multiplex ligation-dependent probe amplification, and reverse transcription-polymerase chain reaction analyses disclosed a large genomic deletion (c.1566-?_1711+?del), leading to the mRNA with loss of the exon 11. Among family members, his son was found to be a carrier of this change, while his parents were negative for the familial CDH1 mutation, implying that this change is a de novo event in the proband. The present report is the first description of a de novo large genomic deletion of CDH1 gene associated with early-onset diffuse gastric cancer. When the clinician finds a relatively-young patient who has multiple SRCCs, CDH1 germline mutation should be considered, even for patients with no familial history.