Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk
Introduction. Critical regulatory genes are functionally silenced by DNA hypermethylation in breast cancer and premalignant lesions. The objective of this study was to examine whether DNA methylation assessed in random fine needle aspirates (rFNA) can be used to inform breast cancer risk. Methods. I...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | The Breast Journal |
| Online Access: | http://dx.doi.org/10.1155/2022/9533461 |
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| author | Kala Visvanathan Ashley Cimino-Mathews Mary Jo Fackler Pritesh S. Karia Christopher J. VandenBussche Mikiaila Orellana Betty May Marissa J. White Mehran Habibi Julie Lange David Euhus Vered Stearns John Fetting Melissa Camp Lisa Jacobs Saraswati Sukumar |
| author_facet | Kala Visvanathan Ashley Cimino-Mathews Mary Jo Fackler Pritesh S. Karia Christopher J. VandenBussche Mikiaila Orellana Betty May Marissa J. White Mehran Habibi Julie Lange David Euhus Vered Stearns John Fetting Melissa Camp Lisa Jacobs Saraswati Sukumar |
| author_sort | Kala Visvanathan |
| collection | DOAJ |
| description | Introduction. Critical regulatory genes are functionally silenced by DNA hypermethylation in breast cancer and premalignant lesions. The objective of this study was to examine whether DNA methylation assessed in random fine needle aspirates (rFNA) can be used to inform breast cancer risk. Methods. In 20 women with invasive breast cancer scheduled for surgery at Johns Hopkins Hospital, cumulative methylation status was assessed in a comprehensive manner. rFNA was performed on tumors, adjacent normal tissues, and all remaining quadrants. Pathology review was conducted on blocks from all excised tissue. The cumulative methylation index (CMI) for 12 genes was assessed by a highly sensitive QM-MSP assay in 280 aspirates and tissue from 11 incidental premalignant lesions. Mann–Whitney and Kruskal Wallis tests were used to compare median CMI by patient, location, and tumor characteristics. Results. The median age of participants was 49 years (interquartile range [IQR]: 44–58). DNA methylation was detectable at high levels in all tumor aspirates (median CMI = 252, IQR: 75–111). Methylation was zero or low in aspirates from adjacent tissue (median CMI = 11, IQR: 0–13), and other quadrants (median CMI = 2, IQR: 1–5). Nineteen incidental lesions were identified in 13 women (4 malignant and 15 premalignant). Median CMI levels were not significantly different in aspirates from quadrants (p=0.43) or adjacent tissue (p=0.93) in which 11 methylated incidental lesions were identified. Conclusions. The diagnostic accuracy of methylation based on rFNA alone to detect premalignant lesions or at-risk quadrants is poor and therefore should not be used to evaluate cancer risk. A more targeted approach needs to be evaluated. |
| format | Article |
| id | doaj-art-4ea84f50b1ae4414a564cb76fefe091d |
| institution | Kabale University |
| issn | 1524-4741 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Breast Journal |
| spelling | doaj-art-4ea84f50b1ae4414a564cb76fefe091d2024-12-02T07:41:35ZengWileyThe Breast Journal1524-47412022-01-01202210.1155/2022/9533461Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer RiskKala Visvanathan0Ashley Cimino-Mathews1Mary Jo Fackler2Pritesh S. Karia3Christopher J. VandenBussche4Mikiaila Orellana5Betty May6Marissa J. White7Mehran Habibi8Julie Lange9David Euhus10Vered Stearns11John Fetting12Melissa Camp13Lisa Jacobs14Saraswati Sukumar15Johns Hopkins Bloomberg School of Public HealthDepartment of PathologyWomen’s Malignancy ProgramJohns Hopkins Bloomberg School of Public HealthDepartment of PathologyJohns Hopkins Bloomberg School of Public HealthJohns Hopkins Bloomberg School of Public HealthDepartment of PathologyDepartment of Surgical OncologyDepartment of Surgical OncologyDepartment of Surgical OncologyWomen’s Malignancy ProgramWomen’s Malignancy ProgramDepartment of Surgical OncologyDepartment of Surgical OncologyWomen’s Malignancy ProgramIntroduction. Critical regulatory genes are functionally silenced by DNA hypermethylation in breast cancer and premalignant lesions. The objective of this study was to examine whether DNA methylation assessed in random fine needle aspirates (rFNA) can be used to inform breast cancer risk. Methods. In 20 women with invasive breast cancer scheduled for surgery at Johns Hopkins Hospital, cumulative methylation status was assessed in a comprehensive manner. rFNA was performed on tumors, adjacent normal tissues, and all remaining quadrants. Pathology review was conducted on blocks from all excised tissue. The cumulative methylation index (CMI) for 12 genes was assessed by a highly sensitive QM-MSP assay in 280 aspirates and tissue from 11 incidental premalignant lesions. Mann–Whitney and Kruskal Wallis tests were used to compare median CMI by patient, location, and tumor characteristics. Results. The median age of participants was 49 years (interquartile range [IQR]: 44–58). DNA methylation was detectable at high levels in all tumor aspirates (median CMI = 252, IQR: 75–111). Methylation was zero or low in aspirates from adjacent tissue (median CMI = 11, IQR: 0–13), and other quadrants (median CMI = 2, IQR: 1–5). Nineteen incidental lesions were identified in 13 women (4 malignant and 15 premalignant). Median CMI levels were not significantly different in aspirates from quadrants (p=0.43) or adjacent tissue (p=0.93) in which 11 methylated incidental lesions were identified. Conclusions. The diagnostic accuracy of methylation based on rFNA alone to detect premalignant lesions or at-risk quadrants is poor and therefore should not be used to evaluate cancer risk. A more targeted approach needs to be evaluated.http://dx.doi.org/10.1155/2022/9533461 |
| spellingShingle | Kala Visvanathan Ashley Cimino-Mathews Mary Jo Fackler Pritesh S. Karia Christopher J. VandenBussche Mikiaila Orellana Betty May Marissa J. White Mehran Habibi Julie Lange David Euhus Vered Stearns John Fetting Melissa Camp Lisa Jacobs Saraswati Sukumar Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk The Breast Journal |
| title | Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk |
| title_full | Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk |
| title_fullStr | Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk |
| title_full_unstemmed | Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk |
| title_short | Evaluating DNA Methylation in Random Fine Needle Aspirates from the Breast to Inform Cancer Risk |
| title_sort | evaluating dna methylation in random fine needle aspirates from the breast to inform cancer risk |
| url | http://dx.doi.org/10.1155/2022/9533461 |
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