Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples
Purpose Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and furt...
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| Format: | Article |
| Language: | English |
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Korean Society of Coloproctology
2022-02-01
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| Series: | Annals of Coloproctology |
| Subjects: | |
| Online Access: | http://coloproctol.org/upload/pdf/ac-2021-00290-0041.pdf |
| _version_ | 1818199549950296064 |
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| author | Sungwon Jung Jong Lyul Lee Tae Won Kim Jongmin Lee Yong Sik Yoon Kil Yeon Lee Ki-hwan Song Chang Sik Yu Yong Beom Cho |
| author_facet | Sungwon Jung Jong Lyul Lee Tae Won Kim Jongmin Lee Yong Sik Yoon Kil Yeon Lee Ki-hwan Song Chang Sik Yu Yong Beom Cho |
| author_sort | Sungwon Jung |
| collection | DOAJ |
| description | Purpose Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC. Methods From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated. Results Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors. Conclusion UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status. |
| first_indexed | 2024-12-12T02:23:32Z |
| format | Article |
| id | doaj.art-26797ad536dd46c981d7ffcfff47295a |
| institution | Directory Open Access Journal |
| issn | 2287-9714 2287-9722 |
| language | English |
| last_indexed | 2024-12-12T02:23:32Z |
| publishDate | 2022-02-01 |
| publisher | Korean Society of Coloproctology |
| record_format | Article |
| series | Annals of Coloproctology |
| spelling | doaj.art-26797ad536dd46c981d7ffcfff47295a2022-12-22T00:41:37ZengKorean Society of ColoproctologyAnnals of Coloproctology2287-97142287-97222022-02-01381728110.3393/ac.2021.00290.00411884Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samplesSungwon Jung0Jong Lyul Lee1Tae Won Kim2Jongmin Lee3Yong Sik Yoon4Kil Yeon Lee5Ki-hwan Song6Chang Sik Yu7Yong Beom Cho8 Department of Genome Medicine and Science, Gachon University College of Medicine, Incheon, Korea Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea Department of Genome Medicine and Science, Gachon University College of Medicine, Incheon, Korea Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea Department of Surgery, Koo Hospital, Daegu, Korea Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, KoreaPurpose Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC. Methods From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated. Results Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors. Conclusion UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.http://coloproctol.org/upload/pdf/ac-2021-00290-0041.pdfulcerative colitiscolorectal neoplasmscolitis-associated neoplasmsgenetic variation |
| spellingShingle | Sungwon Jung Jong Lyul Lee Tae Won Kim Jongmin Lee Yong Sik Yoon Kil Yeon Lee Ki-hwan Song Chang Sik Yu Yong Beom Cho Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples Annals of Coloproctology ulcerative colitis colorectal neoplasms colitis-associated neoplasms genetic variation |
| title | Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples |
| title_full | Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples |
| title_fullStr | Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples |
| title_full_unstemmed | Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples |
| title_short | Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples |
| title_sort | molecular characterization of dysplasia initiated colorectal cancer with assessing matched tumor and dysplasia samples |
| topic | ulcerative colitis colorectal neoplasms colitis-associated neoplasms genetic variation |
| url | http://coloproctol.org/upload/pdf/ac-2021-00290-0041.pdf |
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