Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome
Objective The plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50–75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2019-08-01
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| Series: | BMJ Open Gastroenterology |
| Online Access: | https://bmjopengastro.bmj.com/content/6/1/e000299.full |
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| author | Maria Christensen Andrew E Hendifar Rachel Pearlman Sigurdis Haraldsdottir Albert de la Chapelle Heather Hampel Megan P Hitchins Ingrid P Vogelaar Kevin Brennan Nianmin Zhou Brock Martin Rocio Alvarez Xiaopu Yuan Sungjin Kim Maha Guindi Matthew F Kalady Jennifer DeVecchio James M Church Carrie Snyder Stephen J Lanspa Robert W Haile Henry T Lynch |
| author_facet | Maria Christensen Andrew E Hendifar Rachel Pearlman Sigurdis Haraldsdottir Albert de la Chapelle Heather Hampel Megan P Hitchins Ingrid P Vogelaar Kevin Brennan Nianmin Zhou Brock Martin Rocio Alvarez Xiaopu Yuan Sungjin Kim Maha Guindi Matthew F Kalady Jennifer DeVecchio James M Church Carrie Snyder Stephen J Lanspa Robert W Haile Henry T Lynch |
| author_sort | Maria Christensen |
| collection | DOAJ |
| description | Objective The plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50–75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the most common hereditary CRC condition, has not been assessed. This study sought preliminary evidence for the utility of mSEPT9 for CRC detection in LS.Design Firstly, SEPT9 methylation was measured in LS-associated CRC, advanced adenoma, and subject-matched normal colorectal mucosa tissues by pyrosequencing. Secondly, to detect mSEPT9 as circulating tumor DNA, the plasma-based mSEPT9 test was retrospectively evaluated in LS subjects using the Epi proColon 2.0 CE assay adapted for 1mL plasma using the “1/1 algorithm”. LS case groups included 20 peri-surgical cases with acolonoscopy-based diagnosis of CRC (stages I-IV), 13 post-surgical metastatic CRC, and 17 pre-diagnosis cases. The control group comprised 31 cancer-free LS subjects.Results Differential hypermethylation was found in 97.3% (36/37) of primary CRC and 90.0% (18/20) of advanced adenomas, showing LS-associated neoplasia frequently produce the mSEPT9 biomarker. Sensitivity of plasma mSEPT9 to detect CRC was 70.0% (95% CI, 48%-88%)in cases with a colonoscopy-based CRC diagnosis and 92.3% (95% CI, 64%-100%) inpost-surgical metastatic cases. In pre-diagnosis cases, plasma mSEPT9 was detected within two months prior to colonoscopy-based CRC diagnosis in 3/5 cases. Specificity in controls was 100% (95% CI 89%-100%).Conclusion These preliminary findings suggest mSEPT9 may demonstrate similar diagnostic performance characteristics in LS as in the average-risk population, warranting a well-powered prospective case–control study. |
| format | Article |
| id | doaj-art-9cc419266d314d61ad0f4bf7e132d705 |
| institution | OA Journals |
| issn | 2054-4774 |
| language | English |
| publishDate | 2019-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Gastroenterology |
| spelling | doaj-art-9cc419266d314d61ad0f4bf7e132d7052025-08-20T02:35:44ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742019-08-016110.1136/bmjgast-2019-000299Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndromeMaria Christensen0Andrew E Hendifar1Rachel Pearlman2Sigurdis Haraldsdottir3Albert de la Chapelle4Heather Hampel5Megan P Hitchins6Ingrid P Vogelaar7Kevin Brennan8Nianmin Zhou9Brock Martin10Rocio Alvarez11Xiaopu Yuan12Sungjin Kim13Maha Guindi14Matthew F Kalady15Jennifer DeVecchio16James M Church17Carrie Snyder18Stephen J Lanspa19Robert W Haile20Henry T Lynch211 Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark1 Department of Gastrointestinal Malignancies, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA2 Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USAMedicine, Stanford University, Stanford, California, USADepartment of Internal Medicine and the Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USADepartment of Internal Medicine and the Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USABiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USAMedicine, Stanford University, Stanford, California, USAMedicine, Stanford University, Stanford, California, USAMedicine, Stanford University, Stanford, California, USAMedicine, Stanford University, Stanford, California, USABiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USADepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USAMedicine, Cedars-Sinai Medical Center, Los Angeles, California, USADepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USADepartments of Stem Cell and Regenerative Medicine and Colorectal Surgery, Sanford R Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USADepartment of Stem Cell and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USADepartments of Stem Cell and Regenerative Medicine and Colorectal Surgery, Sanford R Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USAHereditary Cancer Center, Creighton University, Omaha, Nebraska, USAHereditary Cancer Center, Creighton University, Omaha, Nebraska, USADepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USAHereditary Cancer Center, Creighton University, Omaha, Nebraska, USAObjective The plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50–75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the most common hereditary CRC condition, has not been assessed. This study sought preliminary evidence for the utility of mSEPT9 for CRC detection in LS.Design Firstly, SEPT9 methylation was measured in LS-associated CRC, advanced adenoma, and subject-matched normal colorectal mucosa tissues by pyrosequencing. Secondly, to detect mSEPT9 as circulating tumor DNA, the plasma-based mSEPT9 test was retrospectively evaluated in LS subjects using the Epi proColon 2.0 CE assay adapted for 1mL plasma using the “1/1 algorithm”. LS case groups included 20 peri-surgical cases with acolonoscopy-based diagnosis of CRC (stages I-IV), 13 post-surgical metastatic CRC, and 17 pre-diagnosis cases. The control group comprised 31 cancer-free LS subjects.Results Differential hypermethylation was found in 97.3% (36/37) of primary CRC and 90.0% (18/20) of advanced adenomas, showing LS-associated neoplasia frequently produce the mSEPT9 biomarker. Sensitivity of plasma mSEPT9 to detect CRC was 70.0% (95% CI, 48%-88%)in cases with a colonoscopy-based CRC diagnosis and 92.3% (95% CI, 64%-100%) inpost-surgical metastatic cases. In pre-diagnosis cases, plasma mSEPT9 was detected within two months prior to colonoscopy-based CRC diagnosis in 3/5 cases. Specificity in controls was 100% (95% CI 89%-100%).Conclusion These preliminary findings suggest mSEPT9 may demonstrate similar diagnostic performance characteristics in LS as in the average-risk population, warranting a well-powered prospective case–control study.https://bmjopengastro.bmj.com/content/6/1/e000299.full |
| spellingShingle | Maria Christensen Andrew E Hendifar Rachel Pearlman Sigurdis Haraldsdottir Albert de la Chapelle Heather Hampel Megan P Hitchins Ingrid P Vogelaar Kevin Brennan Nianmin Zhou Brock Martin Rocio Alvarez Xiaopu Yuan Sungjin Kim Maha Guindi Matthew F Kalady Jennifer DeVecchio James M Church Carrie Snyder Stephen J Lanspa Robert W Haile Henry T Lynch Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome BMJ Open Gastroenterology |
| title | Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome |
| title_full | Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome |
| title_fullStr | Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome |
| title_full_unstemmed | Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome |
| title_short | Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome |
| title_sort | methylated septin9 plasma test for colorectal cancer detection may be applicable to lynch syndrome |
| url | https://bmjopengastro.bmj.com/content/6/1/e000299.full |
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