Somatic mutations in benign breast disease tissues and association with breast cancer risk

Autor: Stacey J. Winham, Chen Wang, Ethan P. Heinzen, Aditya Bhagwate, Yuanhang Liu, Samantha J. McDonough, Melody L. Stallings-Mann, Marlene H. Frost, Robert A. Vierkant, Lori A. Denison, Jodi M. Carter, Mark E. Sherman, Derek C. Radisky, Amy C. Degnim, Julie M. Cunningham
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: BMC Medical Genomics, Vol 14, Iss 1, Pp 1-12 (2021)
Druh dokumentu: article
ISSN: 1755-8794
DOI: 10.1186/s12920-021-01032-8
Popis: Abstract 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
Databáze: Directory of Open Access Journals
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