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Poster presentations: Genetics 2020

P829 Methylation patterns in dysplasia in inflammatory bowel disease patients

I.A. da Luz Rosa1, P. Silva2, S. Mata3, F. Magro4, F. Carneiro5, A. Peixoto4, M. Silva4, H. Sousa6, J. Roseira6, J. Parra7, R. Barosa8, A. Vieira8, M.J. Brito9, P. Lago10, A. Coelho11, J. Moleiro1, J. Silva1, R. Fonseca3, C. Albuquerque2, A.D. Pereira1

1Grupo de Estudos em Doença Inflamatória Intestinal, 1Instituto Português de Oncologia de Lisboa, Gastroenterology, Lisbon, Portugal, 2Instituto Português de Oncologia de Lisboa, Molecular Pathobiology Investigation Unit, Lisbon, Portugal, 3Instituto Português de Oncologia de Lisboa, Pathology, Lisbon, Portugal, 4Centro Hospitalar de São João, Gastroenterology, Porto, Portugal, 5Centro Hospitalar de São João, Pathology, Porto, Portugal, 6Centro Hospitalar Universitário do Algarve- Unidade de Portimão, Gastroenterology, Portimão, Portugal, 7Centro Hospitalar Universitário do Algarve- Unidade de Portimão, Pathology, Portimão, Portugal, 8Hospital Garcia de Orta, Gastroenterology, Almada, Portugal, 9Hospital Garcia de Orta, Pathology, Almada, Portugal, 10Centro Hospitalar do Porto- EPE–Hospital de Santo António, Gastroenterology, Porto, Portugal, 11Centro Hospitalar do Porto- EPE–Hospital de Santo António, Pathology, Porto, Portugal

Background

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 favours the importance of abnormal DNA methylation in IBD-related carcinogenesis. Our study aimed to define methylation patterns in patients with a 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-nine patients 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 = 0.003) and at dysplasia/cancer diagnosis (p = 0.039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1 genes 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.

Conclusion

Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD– to be further tested in prospective studies.