APC‐related multiple salivary gland lesions: spatial transcriptomic analysis reveals progressive WNT activation
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2025
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| author | Fiona Chan‐Pak‐Choon Catherine Beaumont José Camacho Valenzuela Josianne Leblanc Sonja Dahlum Reiner Siebert François Thuot Marc Pusztaszeri Jacinthe Chênevert Paz Polak Tania Cruz Marino Barbara Rivera William D. Foulkes |
| author_facet | Fiona Chan‐Pak‐Choon Catherine Beaumont José Camacho Valenzuela Josianne Leblanc Sonja Dahlum Reiner Siebert François Thuot Marc Pusztaszeri Jacinthe Chênevert Paz Polak Tania Cruz Marino Barbara Rivera William D. Foulkes Fiona Chan‐Pak‐Choon Catherine Beaumont José Camacho Valenzuela Josianne Leblanc Sonja Dahlum Reiner Siebert François Thuot Marc Pusztaszeri Jacinthe Chênevert Paz Polak Tania Cruz Marino Barbara Rivera William D. Foulkes |
| collection | Wiley Open Access |
| contents | APC‐related multiple salivary gland lesions: spatial transcriptomic analysis reveals progressive WNT activation Fiona Chan‐Pak‐Choon Catherine Beaumont José Camacho Valenzuela Josianne Leblanc Sonja Dahlum Reiner Siebert François Thuot Marc Pusztaszeri Jacinthe Chênevert Paz Polak Tania Cruz Marino Barbara Rivera William D. Foulkes The Journal of Pathology AbstractAttenuated familial adenomatous polyposis (AFAP) is a disorder caused by germline pathogenic variants in APC and is characterized by the presence of <100 colonic polyps and a high lifetime risk of developing colorectal cancer. Salivary gland basal cell tumours are uncommon and have not previously been reported in AFAP. We present a family with AFAP and multiple salivary gland tumours, including basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC). The colon and salivary gland tumours showed abnormal nuclear β‐catenin staining. Genomic analysis of both parotid BCACs showed copy‐number‐neutral loss of heterozygosity (CNN‐LOH) at the APC locus, implicating loss of full‐length APC in the aetiology of parotid BCACs. In contrast, the submandibular BCAC showed a p.(Ile35Thr) CTNNB1 mutation. Spatial transcriptomic analysis revealed a stepwise increase in the expression of WNT pathway genes across the proband's salivary lesions, from benign (intercalated duct hyperplasia and BCAs) to malignant (BCACs). Our results showcase BCA and BCAC as potential new phenotypes of AFAP. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6466 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1002/path.6466 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6466 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | APC‐related multiple salivary gland lesions: spatial transcriptomic analysis reveals progressive WNT activation Fiona Chan‐Pak‐Choon Catherine Beaumont José Camacho Valenzuela Josianne Leblanc Sonja Dahlum Reiner Siebert François Thuot Marc Pusztaszeri Jacinthe Chênevert Paz Polak Tania Cruz Marino Barbara Rivera William D. Foulkes The Journal of Pathology APC‐related multiple salivary gland lesions: spatial transcriptomic analysis reveals progressive WNT activation Fiona Chan‐Pak‐Choon Catherine Beaumont José Camacho Valenzuela Josianne Leblanc Sonja Dahlum Reiner Siebert François Thuot Marc Pusztaszeri Jacinthe Chênevert Paz Polak Tania Cruz Marino Barbara Rivera William D. Foulkes The Journal of Pathology AbstractAttenuated familial adenomatous polyposis (AFAP) is a disorder caused by germline pathogenic variants in APC and is characterized by the presence of <100 colonic polyps and a high lifetime risk of developing colorectal cancer. Salivary gland basal cell tumours are uncommon and have not previously been reported in AFAP. We present a family with AFAP and multiple salivary gland tumours, including basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC). The colon and salivary gland tumours showed abnormal nuclear β‐catenin staining. Genomic analysis of both parotid BCACs showed copy‐number‐neutral loss of heterozygosity (CNN‐LOH) at the APC locus, implicating loss of full‐length APC in the aetiology of parotid BCACs. In contrast, the submandibular BCAC showed a p.(Ile35Thr) CTNNB1 mutation. Spatial transcriptomic analysis revealed a stepwise increase in the expression of WNT pathway genes across the proband's salivary lesions, from benign (intercalated duct hyperplasia and BCAs) to malignant (BCACs). Our results showcase BCA and BCAC as potential new phenotypes of AFAP. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6466 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | APC‐related multiple salivary gland lesions: spatial transcriptomic analysis reveals progressive WNT activation |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6466 |