A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines
| Autor: | Lind, Guro E, Thorstensen, Lin, Løvig, Tone, Meling, Gunn I, Hamelin, Richard, Rognum, Torleiv O, Esteller, Manel, Lothe, Ragnhild A |
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| Přispěvatelé: | Department of Genetics, Norwegian Radium Hospital-Institute for Cancer Research, Institute of Forensic Medicine, University of Oslo (UiO)-National Hospital, Akershus University Hospital [Lørenskog], Instabilité des microsatellites et cancers [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cancer Epigenetics Laboratory, Spanish National Cancer Research Center (CNIO), GEL is a Research Fellow and LT a Post-Doctoral Fellow of the Norwegian Cancer Society. TL is Post-Doctoral Fellow of the Norwegian Foundation for Health and Rehabilitation. The study was funded by grants from the Norwegian Cancer Society (A95068 and D97127 RAL)., Instabilité des microsatellites et cancers [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Maylin, Françoise |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
MGMT MESH: Neoplasm Proteins hMLH1 p16 [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology MESH: Cadherins p14 MESH: DNA Methylation Tumor Suppressor Protein p14ARF TP53 colorectal carcinomas Promoter Regions Genetic MESH: CpG Islands E-cadherin MESH: Genes APC Nuclear Proteins MESH: Comparative Study Cadherins lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens MESH: Nu Neoplasm Proteins MESH: Cyclin-Dependent Kinase Inhibitor p16 Colonic Neoplasms CpG methylation Female Colorectal Neoplasms MutL Protein Homolog 1 Genes APC MESH: Cell Line Tumor KRAS MESH: Carrier Proteins [SDV.CAN]Life Sciences [q-bio]/Cancer lcsh:RC254-282 O(6)-Methylguanine-DNA Methyltransferase Sex Factors [SDV.CAN] Life Sciences [q-bio]/Cancer Cell Line Tumor [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology colon cancer cell lines Humans APC [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology neoplasms Cyclin-Dependent Kinase Inhibitor p16 MSI Adaptor Proteins Signal Transducing MSS MESH: Colonic Neoplasms MESH: Humans Research DNA Methylation [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology digestive system diseases MESH: Male CpG Islands MESH: Microsatellite Repeats Carrier Proteins MESH: Female MESH: Colorectal Neoplasms Microsatellite Repeats |
| Zdroj: | Molecular cancer [electronic resource] Molecular cancer [electronic resource], 2004, 3, pp.28. ⟨10.1186/1476-4598-3-28⟩ Molecular Cancer, Vol 3, Iss 1, p 28 (2004) Molecular Cancer |
| Popis: | Background Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS) and 9 microsatellite unstable (MSI) colon cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI) with known ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the promoter methylation of the following genes: hMLH1, MGMT, p16INK4a (CDKN2A α-transcript), p14ARF (CDKN2A β-transcript), APC, and E-cadherin (CDH1). We compared the DNA methylation profiles of the cell lines with those of the primary tumors. Finally, we examined if the epigenetic changes were associated with known genetic markers and/or clinicopathological variables. Results The cell lines and primary tumors generally showed similar overall distribution and frequencies of gene methylation. Among the cell lines, 15%, 50%, 75%, 65%, 20% and 15% showed promoter methylation for hMLH1, MGMT, p16INK4a, p14ARF, APC, and E-cadherin, respectively, whereas 21%, 40%, 32%, 38%, 32%, and 40% of the primary tumors were methylated for the same genes. hMLH1 and p14ARF were significantly more often methylated in MSI than in MSS primary tumors, whereas the remaining four genes showed similar methylation frequencies in the two groups. Methylation of p14ARF, which indirectly inactivates TP53, was seen more frequently in tumors with normal TP53 than in mutated samples, but the difference was not statistically significant. Methylation of p14ARF and p16INK4a was often present in the same primary tumors, but association to diploidy, MSI, right-sided location and female gender was only significant for p14ARF. E-cadherin was methylated in 14/34 tumors with altered APC further stimulating WNT signaling. Conclusions The present study shows that colon cancer cell lines are in general relevant in vitro models, comparable with the in vivo situation, as the cell lines display many of the same molecular alterations as do the primary carcinomas. The combined pattern of epigenetic and genetic aberrations in the primary carcinomas reveals associations between them as well as to clinicopathological variables, and may aid in the future molecular assisted classification of clinically distinct stages. |
| Databáze: | OpenAIRE |
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