The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer Susceptibility
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 asso...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/12/2213 |
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| author | Jihenne Ben Aissa-Haj Hugo Pinheiro François Cornelis Molka Sebai Didier Meseure Adrien Briaux Philippe Berteaux Cedric Lefol Gaëtan Des Guetz Martine Trassard Denise Stevens François Vialard Ivan Bieche Catherine Noguès Roseline Tang Carla Oliveira Dominique Stoppat-Lyonnet Rosette Lidereau Etienne Rouleau |
| author_facet | Jihenne Ben Aissa-Haj Hugo Pinheiro François Cornelis Molka Sebai Didier Meseure Adrien Briaux Philippe Berteaux Cedric Lefol Gaëtan Des Guetz Martine Trassard Denise Stevens François Vialard Ivan Bieche Catherine Noguès Roseline Tang Carla Oliveira Dominique Stoppat-Lyonnet Rosette Lidereau Etienne Rouleau |
| author_sort | Jihenne Ben Aissa-Haj |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T16:30:07Z |
| format | Article |
| id | doaj.art-23af24f8644445f5be50c9ee08c1f2ab |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T16:30:07Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-23af24f8644445f5be50c9ee08c1f2ab2023-11-24T15:02:54ZengMDPI AGGenes2073-44252022-11-011312221310.3390/genes13122213The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer SusceptibilityJihenne Ben Aissa-Haj0Hugo Pinheiro1François Cornelis2Molka Sebai3Didier Meseure4Adrien Briaux5Philippe Berteaux6Cedric Lefol7Gaëtan Des Guetz8Martine Trassard9Denise Stevens10François Vialard11Ivan Bieche12Catherine Noguès13Roseline Tang14Carla Oliveira15Dominique Stoppat-Lyonnet16Rosette Lidereau17Etienne Rouleau18Department of Human and Experimental Pathology, Institut Pasteur de Tunis, Tunis 1002, TunisiaFaculty of Medicine, University of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, PortugalUniversity Hospital Center Gabriel-Montpied, Clermont-Ferrand, 58 Rue Montalembert, 63000 Clermont-Ferrand, FranceDepartment of Biology and Pathology, Laboratory of Cancer Genetics Institut Gustave Roussy, 94805 Villejuif, FranceAnatomopathological Service, Curie Institute, 26 Rue d’Ulm, 75005 Paris, FranceOncogenetic Laboratory, Departement of Genetics, Curie Institute, 26 Rue d’Ulm, 75005 Paris, FranceUniversity Hospital Center Gabriel-Montpied, Clermont-Ferrand, 58 Rue Montalembert, 63000 Clermont-Ferrand, FranceCentre Leon Berard, 28 Promenade Léa et Napoléon Bullukian, 96008 Lyon, FranceMedical Oncology Department, Delafontaine Hospital, 93200 St. Denis, FranceAnatomopathological Service, Curie Institute, 26 Rue d’Ulm, 75005 Paris, FranceBiostatistic Service, René Huguenin Hospital, Curie Institute, 35 rue Dailly, 92210 Saint Cloud, FranceGenetics Department, Intermunicipal Hospital Center Poissy St. Germain-en-Laye, 78300 Poissy, FranceOncogenetic Laboratory, Departement of Genetics, Curie Institute, 26 Rue d’Ulm, 75005 Paris, FranceDepartment of Cancer Anticipation and Monitoring, Clinical Oncogenetics, Paoli-Calmettes Institute, 13009 Marseille, FranceDepartment of Biology and Pathology, Laboratory of Cancer Genetics Institut Gustave Roussy, 94805 Villejuif, FranceFaculty of Medicine, University of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, PortugalOncogenetic Laboratory, Departement of Genetics, Curie Institute, 26 Rue d’Ulm, 75005 Paris, FranceOncogenetic Laboratory, Departement of Genetics, Curie Institute, 26 Rue d’Ulm, 75005 Paris, FranceDepartment of Biology and Pathology, Laboratory of Cancer Genetics Institut Gustave Roussy, 94805 Villejuif, FranceE-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.https://www.mdpi.com/2073-4425/13/12/2213breast carcinomagastric carcinoma<i>CDH1</i> rearrangementsCNVCGH array<i>BRCA1/2</i> negative cases |
| spellingShingle | Jihenne Ben Aissa-Haj Hugo Pinheiro François Cornelis Molka Sebai Didier Meseure Adrien Briaux Philippe Berteaux Cedric Lefol Gaëtan Des Guetz Martine Trassard Denise Stevens François Vialard Ivan Bieche Catherine Noguès Roseline Tang Carla Oliveira Dominique Stoppat-Lyonnet Rosette Lidereau Etienne Rouleau The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer Susceptibility Genes breast carcinoma gastric carcinoma <i>CDH1</i> rearrangements CNV CGH array <i>BRCA1/2</i> negative cases |
| title | The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer Susceptibility |
| title_full | The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer Susceptibility |
| title_fullStr | The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer Susceptibility |
| title_full_unstemmed | The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer Susceptibility |
| title_short | The Identification of Large Rearrangements Involving Intron 2 of the <i>CDH1</i> Gene in <i>BRCA1/2</i> Negative and Breast Cancer Susceptibility |
| title_sort | identification of large rearrangements involving intron 2 of the i cdh1 i gene in i brca1 2 i negative and breast cancer susceptibility |
| topic | breast carcinoma gastric carcinoma <i>CDH1</i> rearrangements CNV CGH array <i>BRCA1/2</i> negative cases |
| url | https://www.mdpi.com/2073-4425/13/12/2213 |
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