Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesis
<p>Abstract</p> <p>Background</p> <p>Tumor-derived aberrantly methylated DNA might serve as diagnostic biomarkers for cancer, but so far, few such markers have been identified. The aim of the present study was to investigate the potential of the <it>MAL </it>...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-03-01
|
| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/6/1/13 |
| _version_ | 1811251575834804224 |
|---|---|
| author | Kallioniemi Anne Alonso Miguel A Eknæs Mette Berg Marianne Kolberg Matthias Ahlquist Terje Lind Guro E Meling Gunn I Skotheim Rolf I Rognum Torleiv O Thiis-Evensen Espen Lothe Ragnhild A |
| author_facet | Kallioniemi Anne Alonso Miguel A Eknæs Mette Berg Marianne Kolberg Matthias Ahlquist Terje Lind Guro E Meling Gunn I Skotheim Rolf I Rognum Torleiv O Thiis-Evensen Espen Lothe Ragnhild A |
| author_sort | Kallioniemi Anne |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Tumor-derived aberrantly methylated DNA might serve as diagnostic biomarkers for cancer, but so far, few such markers have been identified. The aim of the present study was to investigate the potential of the <it>MAL </it>(T-cell differentiation protein) gene as an early epigenetic diagnostic marker for colorectal tumors.</p> <p>Methods</p> <p>Using methylation-specific polymerase chain reaction (MSP) the promoter methylation status of <it>MAL </it>was analyzed in 218 samples, including normal mucosa (n = 44), colorectal adenomas (n = 63), carcinomas (n = 65), and various cancer cell lines (n = 46). Direct bisulphite sequencing was performed to confirm the MSP results. <it>MAL </it>gene expression was investigated with real time quantitative analyses before and after epigenetic drug treatment. Immunohistochemical analysis of MAL was done using normal colon mucosa samples (n = 5) and a tissue microarray with 292 colorectal tumors.</p> <p>Results</p> <p>Bisulphite sequencing revealed that the methylation was unequally distributed within the <it>MAL </it>promoter and by MSP analysis a region close to the transcription start point was shown to be hypermethylated in the majority of colorectal carcinomas (49/61, 80%) as well as in adenomas (45/63, 71%). In contrast, only a minority of the normal mucosa samples displayed hypermethylation (1/23, 4%). The hypermethylation of <it>MAL </it>was significantly associated with reduced or lost gene expression in <it>in vitro </it>models. Furthermore, removal of the methylation re-induced gene expression in colon cancer cell lines. Finally, MAL protein was expressed in epithelial cells of normal colon mucosa, but not in the malignant cells of the same type.</p> <p>Conclusion</p> <p>Promoter hypermethylation of <it>MAL </it>was present in the vast majority of benign and malignant colorectal tumors, and only rarely in normal mucosa, which makes it suitable as a diagnostic marker for early colorectal tumorigenesis.</p> |
| first_indexed | 2024-04-12T16:22:29Z |
| format | Article |
| id | doaj.art-fe8f6a4f44d24e4dada3ede8e6d8589f |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T16:22:29Z |
| publishDate | 2008-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-fe8f6a4f44d24e4dada3ede8e6d8589f2022-12-22T03:25:31ZengBMCJournal of Translational Medicine1479-58762008-03-01611310.1186/1479-5876-6-13Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesisKallioniemi AnneAlonso Miguel AEknæs MetteBerg MarianneKolberg MatthiasAhlquist TerjeLind Guro EMeling Gunn ISkotheim Rolf IRognum Torleiv OThiis-Evensen EspenLothe Ragnhild A<p>Abstract</p> <p>Background</p> <p>Tumor-derived aberrantly methylated DNA might serve as diagnostic biomarkers for cancer, but so far, few such markers have been identified. The aim of the present study was to investigate the potential of the <it>MAL </it>(T-cell differentiation protein) gene as an early epigenetic diagnostic marker for colorectal tumors.</p> <p>Methods</p> <p>Using methylation-specific polymerase chain reaction (MSP) the promoter methylation status of <it>MAL </it>was analyzed in 218 samples, including normal mucosa (n = 44), colorectal adenomas (n = 63), carcinomas (n = 65), and various cancer cell lines (n = 46). Direct bisulphite sequencing was performed to confirm the MSP results. <it>MAL </it>gene expression was investigated with real time quantitative analyses before and after epigenetic drug treatment. Immunohistochemical analysis of MAL was done using normal colon mucosa samples (n = 5) and a tissue microarray with 292 colorectal tumors.</p> <p>Results</p> <p>Bisulphite sequencing revealed that the methylation was unequally distributed within the <it>MAL </it>promoter and by MSP analysis a region close to the transcription start point was shown to be hypermethylated in the majority of colorectal carcinomas (49/61, 80%) as well as in adenomas (45/63, 71%). In contrast, only a minority of the normal mucosa samples displayed hypermethylation (1/23, 4%). The hypermethylation of <it>MAL </it>was significantly associated with reduced or lost gene expression in <it>in vitro </it>models. Furthermore, removal of the methylation re-induced gene expression in colon cancer cell lines. Finally, MAL protein was expressed in epithelial cells of normal colon mucosa, but not in the malignant cells of the same type.</p> <p>Conclusion</p> <p>Promoter hypermethylation of <it>MAL </it>was present in the vast majority of benign and malignant colorectal tumors, and only rarely in normal mucosa, which makes it suitable as a diagnostic marker for early colorectal tumorigenesis.</p>http://www.translational-medicine.com/content/6/1/13 |
| spellingShingle | Kallioniemi Anne Alonso Miguel A Eknæs Mette Berg Marianne Kolberg Matthias Ahlquist Terje Lind Guro E Meling Gunn I Skotheim Rolf I Rognum Torleiv O Thiis-Evensen Espen Lothe Ragnhild A Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesis Journal of Translational Medicine |
| title | Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesis |
| title_full | Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesis |
| title_fullStr | Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesis |
| title_full_unstemmed | Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesis |
| title_short | Hypermethylated <it>MAL </it>gene – a silent marker of early colon tumorigenesis |
| title_sort | hypermethylated it mal it gene a silent marker of early colon tumorigenesis |
| url | http://www.translational-medicine.com/content/6/1/13 |
| work_keys_str_mv | AT kallioniemianne hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT alonsomiguela hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT eknæsmette hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT bergmarianne hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT kolbergmatthias hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT ahlquistterje hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT lindguroe hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT melinggunni hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT skotheimrolfi hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT rognumtorleivo hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT thiisevensenespen hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis AT lotheragnhilda hypermethylateditmalitgeneasilentmarkerofearlycolontumorigenesis |