Isadora Rosa1, Patrícia Silva2, Sara da Mata3, Fernando Magro4, Fátima Carneiro5, Armando Peixoto4, Marco Silva4, Helena T Sousa6,7, Joana Roseira6,7, José Parra8, Rita Barosa9, Ana Vieira9, Maria José Brito10, Paula Lago11, André Coelho12, Joana Moleiro1, João Pereira da Silva1, Ricardo Fonseca3, Cristina Albuquerque2, A Dias Pereira1. 1. Gastroenterology Department, Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE, Lisboa, Portugal. 2. Molecular Pathobiology Investigation Unit, Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE, Lisboa, Portugal. 3. Pathology Department, Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE, Lisboa, Portugal. 4. Gastroenterology Department, Centro Hospitalar de São João, EPE, Porto, Portugal. 5. Pathology Department, Centro Hospitalar de São João, EPE, Porto, Portugal. 6. Gastroenterology Department, Centro Hospitalar Universitário do Algarve, EPE, Unidade de Portimão, Portimão, Portugal. 7. Algarve Biomedical Center, Campus Gambelas - Universidade do Algarve, Faro, Portugal. 8. Pathology Department, Centro Hospitalar Universitário do Algarve, EPE, Unidade de Portimão, Portimão, Portugal. 9. Gastroenterology Department, Hospital Garcia de Orta, EPE, Almada, Portugal. 10. Pathology Department, Hospital Garcia de Orta, EPE, Almada, Portugal. 11. Gastroenterology Department, Centro Hospitalar do Porto, EPE - Hospital de Santo António, Porto, Portugal. 12. Portuguese Inflammatory Bowel Diseases Study Group, Porto, Portugal.
Abstract
Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis. Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification. Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.
Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBDpatients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis. Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification. Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.
Authors: Qiyuan Han; Thomas J Y Kono; Charles G Knutson; Nicola M Parry; Christopher L Seiler; James G Fox; Steven R Tannenbaum; Natalia Y Tretyakova Journal: Int J Mol Sci Date: 2020-12-31 Impact factor: 5.923