| Summary: | E-cadherin, a <i>CDH1</i> gene product, is a calcium-dependent cell–cell adhesion molecule playing a critical role in the establishment of epithelial architecture, maintenance of cell polarity, and differentiation. Germline pathogenic variants in the <i>CDH1</i> gene are associated with hereditary diffuse gastric cancer (HDGC), and large rearrangements in the <i>CDH1</i> gene are now being reported as well. Because <i>CDH1</i> pathogenic variants could be associated with breast cancer (BC) susceptibility, <i>CDH1</i> rearrangements could also impact it. The aim of our study is to identify rearrangements in the <i>CDH1</i> gene in 148 BC cases with no <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants. To do so, a zoom-in CGH array, covering the exonic, intronic, and flanking regions of the <i>CDH1</i> gene, was used to screen our cohort. Intron 2 of the <i>CDH1</i> gene was specifically targeted because it is largely reported to include several regulatory regions. As results, we detected one large rearrangement causing a premature stop in exon 3 of the <i>CDH1</i> gene in a proband with a bilateral lobular breast carcinoma and a gastric carcinoma (GC). Two large rearrangements in the intron 2, a deletion and a duplication, were also reported only with BC cases without any familial history of GC. No germline rearrangements in the <i>CDH1</i> coding region were detected in those families without GC and with a broad range of BC susceptibility. This study confirms the diversity of large rearrangements in the <i>CDH1</i> gene. The rearrangements identified in intron 2 highlight the putative role of this intron in <i>CDH1</i> regulation and alternative transcripts. Recurrent duplication copy number variations (CNV) are found in this region, and the deletion encompasses an alternative <i>CDH1</i> transcript. Screening for large rearrangements in the <i>CDH1</i> gene could be important for genetic testing of BC.
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