دورية أكاديمية
Somatic mutations in benign breast disease tissues and association with breast cancer risk.
| العنوان: | Somatic mutations in benign breast disease tissues and association with breast cancer risk. |
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| المؤلفون: | Winham SJ; Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Winham.stacey@mayo.edu., Wang C; Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Heinzen EP; Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Bhagwate A; Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Liu Y; Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., McDonough SJ; Medical Genome Facility, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Stallings-Mann ML; Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA., Frost MH; Women's Cancer Program, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Vierkant RA; Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Denison LA; Information Technology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Carter JM; Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Sherman ME; Epidemiology and Laboratory Medicine and Pathology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA., Radisky DC; Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA., Degnim AC; Breast, Endocrine, Metabolic and GI Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Cunningham JM; Experimental Pathology and Laboratory Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. |
| المصدر: | BMC medical genomics [BMC Med Genomics] 2021 Jul 14; Vol. 14 (1), pp. 185. Date of Electronic Publication: 2021 Jul 14. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101319628 Publication Model: Electronic Cited Medium: Internet ISSN: 1755-8794 (Electronic) Linking ISSN: 17558794 NLM ISO Abbreviation: BMC Med Genomics Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central |
| مواضيع طبية MeSH: | Breast Neoplasms* |
| مستخلص: | Background: Benign breast disease (BBD) is a risk factor for breast cancer (BC); however, little is known about the genetic alterations present at the time of BBD diagnosis and how these relate to risk of incident BC. Methods: A subset of a long-term BBD cohort was selected to examine DNA variation across three BBD groups (42 future estrogen receptor-positive (ER+) BC, 36 future estrogen receptor-negative (ER-) BC, and 42 controls cancer-free for at least 16 years post-BBD). DNA extracted from archival formalin fixed, paraffin-embedded (FFPE) tissue blocks was analyzed for presence of DNA alterations using a targeted panel of 93 BC-associated genes. To address artifacts frequently observed in FFPE tissues (e.g., C>T changes), we applied three filtering strategies based on alternative allele frequencies and nucleotide substitution context. Gene-level associations were performed using two types of burden tests and adjusted for clinical and technical covariates. Results: After filtering, the variant frequency of SNPs in our sample was highly consistent with population allele frequencies reported in 1 KG/ExAC (0.986, p < 1e-16). The top ten genes found to be nominally associated with later cancer status by four of 12 association methods(p < 0.05) were MED12, MSH2, BRIP1, PMS1, GATA3, MUC16, FAM175A, EXT2, MLH1 and TGFB1, although these were not statistically significant in permutation testing. However, all 10 gene-level associations had OR < 1 with lower mutation burden in controls compared to cases, which was marginally statistically significant in permutation testing (p = 0.04). Comparing between the three case groups, BBD ER+ cases were closer to controls in mutation profile, while BBD ER- cases were distinct. Notably, the variant burden was significantly higher in controls than in either ER+ or ER- cases. CD45 expression was associated with mutational burden (p < 0.001). Conclusions: Somatic mutations were more frequent in benign breast tissue from women who did not develop cancer, opening questions of clonal diversity or immune-mediated restraint on future cancer development. CD45 expression was positively associated with mutational burden, most strongly in controls. Further studies in both normal and premalignant tissues are needed to better understand the role of somatic gene mutations and their contribution to future cancer development. (© 2021. The Author(s).) |
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| معلومات مُعتمدة: | P30 CA015083 United States CA NCI NIH HHS; R01CA187112 National Cancer Institute (US) |
| فهرسة مساهمة: | Keywords: Benign breast disease; Breast cancer risk; CD45 expression; Mutation burden; Somatic mutations |
| تواريخ الأحداث: | Date Created: 20210715 Date Completed: 20220119 Latest Revision: 20220119 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8278587 |
| DOI: | 10.1186/s12920-021-01032-8 |
| PMID: | 34261476 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1755-8794 |
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| DOI: | 10.1186/s12920-021-01032-8 |