Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP)
Background: The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patien...
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3487 |
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| author | Shih-Ching Chang Anna Fen-Yau Li Pei-Ching Lin Chun-Chi Lin Hung-Hsin Lin Shen-Chieh Huang Chien-Hsing Lin Wen-Yi Liang Wei-Shone Chen Jeng-Kai Jiang Jen-Kou Lin Shung-Haur Yang Yuan-Tzu Lan |
| author_facet | Shih-Ching Chang Anna Fen-Yau Li Pei-Ching Lin Chun-Chi Lin Hung-Hsin Lin Shen-Chieh Huang Chien-Hsing Lin Wen-Yi Liang Wei-Shone Chen Jeng-Kai Jiang Jen-Kou Lin Shung-Haur Yang Yuan-Tzu Lan |
| author_sort | Shih-Ching Chang |
| collection | DOAJ |
| description | Background: The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS. Results: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of <i>BRAF</i>, <i>POLD1</i>, <i>MSH3</i>, and <i>SMAD4</i> mutations but lower frequencies of <i>APC</i>, <i>TP53</i>, and <i>KRAS</i> mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors. Conclusions: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features. |
| first_indexed | 2024-03-10T14:38:28Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:38:28Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f502b4a68bc34afa846babb446b1f8db2023-11-20T22:02:39ZengMDPI AGCancers2072-66942020-11-011211348710.3390/cancers12113487Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP)Shih-Ching Chang0Anna Fen-Yau Li1Pei-Ching Lin2Chun-Chi Lin3Hung-Hsin Lin4Shen-Chieh Huang5Chien-Hsing Lin6Wen-Yi Liang7Wei-Shone Chen8Jeng-Kai Jiang9Jen-Kou Lin10Shung-Haur Yang11Yuan-Tzu Lan12Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDepartment of Pathology, Taipei Veterans General Hospital, Taipei 11217, TaiwanDepartment of Clinical Pathology, Yang-Ming Branch, Taipei City Hospital, Taipei 11146, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Genomic Medicine, National Health Research Institutes, Zhunan 35053, TaiwanDepartment of Pathology, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanDivision of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanBackground: The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS. Results: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of <i>BRAF</i>, <i>POLD1</i>, <i>MSH3</i>, and <i>SMAD4</i> mutations but lower frequencies of <i>APC</i>, <i>TP53</i>, and <i>KRAS</i> mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors. Conclusions: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features.https://www.mdpi.com/2072-6694/12/11/3487colorectal cancermicrosatellite instabilitymutationCpG island methylator phenotype |
| spellingShingle | Shih-Ching Chang Anna Fen-Yau Li Pei-Ching Lin Chun-Chi Lin Hung-Hsin Lin Shen-Chieh Huang Chien-Hsing Lin Wen-Yi Liang Wei-Shone Chen Jeng-Kai Jiang Jen-Kou Lin Shung-Haur Yang Yuan-Tzu Lan Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP) Cancers colorectal cancer microsatellite instability mutation CpG island methylator phenotype |
| title | Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP) |
| title_full | Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP) |
| title_fullStr | Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP) |
| title_full_unstemmed | Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP) |
| title_short | Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP) |
| title_sort | clinicopathological and molecular profiles of sporadic microsatellite unstable colorectal cancer with or without the cpg island methylator phenotype cimp |
| topic | colorectal cancer microsatellite instability mutation CpG island methylator phenotype |
| url | https://www.mdpi.com/2072-6694/12/11/3487 |
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