Constitutional epimutations in LTBP4, a component of the TGF-β signaling, and in BRCA1, as potential drivers of early-onset colorectal cancer
Our findings suggest that constitutional methylation of LTBP4 CpG island 102 may be associated with increased CRC risk. Identification of additional cases is needed to confirm the existence of a novel CRC predisposition syndrome driven by epigenetic inactivation of LTBP4, potentially also linked to other clinical phenotypes associated with LTBP4 deficiency, such as pulmonary emphysema. Whether constitutional BRCA1 methylation contributes to CRC risk remains to be determined.
Authors
- Mariona Terradas (ORCID: https://orcid.org/0000-0001-7813-1172)
- Julen Viana-Errasti (ORCID: https://orcid.org/0000-0002-9672-6951)
- Pablo Bousquets‐Muñoz (ORCID: https://orcid.org/0000-0002-2969-008X)
- Noah C. Helderman (ORCID: https://orcid.org/0000-0001-9089-8907)
- Tom van Wezel (ORCID: https://orcid.org/0000-0001-5773-7730)
- Gabriel Capellá (ORCID: https://orcid.org/0000-0002-4669-7320)
- Francisco D. Morón-Duran (ORCID: https://orcid.org/0000-0003-3097-7675)
- Vı́ctor Moreno (ORCID: https://orcid.org/0000-0002-2818-5487)
- Maartje Nielsen (ORCID: https://orcid.org/0000-0002-5351-1870)
- Conxi Lázaro (ORCID: https://orcid.org/0000-0002-7198-5906)
- Jakob Nikolas Kather (ORCID: https://orcid.org/0000-0002-3730-5348)
- Diantha Terlouw (ORCID: https://orcid.org/0000-0002-8090-8806)
- Laura Valle (ORCID: https://orcid.org/0000-0003-0371-0844)
- Pilar Mur (ORCID: https://orcid.org/0000-0003-0780-926X)
- Xosé S. Puente (ORCID: https://orcid.org/0000-0001-9525-1483)
- Chiara Maria Lavinia Löffler
- Xavier Sanjuán
- Pol Mengod
Institutions
- Universitat Autònoma de Barcelona (ES)
- Universidad de Oviedo (ES)
- Heidelberg University (DE)
- Leiden University Medical Center (NL)
- Helmholtz-Zentrum Dresden-Rossendorf (DE)
- Bellvitge University Hospital (ES)
- University Hospital Heidelberg (DE)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Ajuntament de L’Hospitalet (ES)
- Institut Català d'Oncologia (ES)
- National Center for Tumor Diseases (DE)
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- University Hospital Carl Gustav Carus (DE)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Clinical Epigenetics
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1186/s13148-025-01924-x
- Citations
- 1
- Primary Topic
- Genetic factors in colorectal cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.47
Funders
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Centro de Investigación Biomédica en Red de Cáncer
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación