High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing
High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing
Abstract The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor and peripheral blood from 52 reportedly sporadic breast cancer patients, including breast-conserving surgery cases. Targeted resequencing of 542 cancer associated genes revealed mosaic somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3 and TSHR in the normal mammary gland, at considerable allelic frequencies (9×10?2 to 5.2×10?1) indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low level-mosaic (in 10?2 to 10?4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumor mammary gland tissue of breast-conserving surgery patients.
Buckley Patrick G.、Kostecka Anna、Nowikiewicz Tomasz、Olszewski Pawe?、Mair Theresa、Gucwa Magdalena、Hartman Johan、Zegarski Wojciech、Tiemann-Boege Irene、Dumanski Jan P.、Jankowski Micha?、Skokowski Jaros?aw、Koczkowska Magdalena、Madanecki Piotr、P?ksa Rafa?、Heinzl Monika、Salazar Renato、?rutek Ewa、Andreou Maria、Horbacz Monika、Piotrowski Arkadiusz、Davies Hanna、Szylberg ?ukasz
Genuity Science Genomics CentreFaculty of Pharmacy, Medical University of Gdansk||3P Medicine Lab, Medical University of GdanskDepartment of Surgical Oncology, Ludwik Rydygier?ˉs Collegium Medicum UMK||Department of Breast Cancer and Reconstructive Surgery, Prof. F. Lukaszczyk Oncology Center3P Medicine Lab, Medical University of GdanskInstitute of Biophysics, Johannes Kepler UniversityFaculty of Pharmacy, Medical University of GdanskDepartment of Oncology and Pathology, Karolinska Institutet||Department of Pathology, Karolinska University Hospital||MedTech Labs, Bioclinicum, Karolinska University HospitalDepartment of Surgical Oncology, Ludwik Rydygier?ˉs Collegium Medicum UMKInstitute of Biophysics, Johannes Kepler University3P Medicine Lab, Medical University of Gdansk||Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDepartment of Surgical Oncology, Ludwik Rydygier?ˉs Collegium Medicum UMKDepartment of Surgical Oncology, Medical University of GdanskFaculty of Pharmacy, Medical University of Gdansk||3P Medicine Lab, Medical University of GdanskFaculty of Pharmacy, Medical University of GdanskDepartment of Patomorphology, Medical University of GdanskInstitute of Biophysics, Johannes Kepler UniversityInstitute of Biophysics, Johannes Kepler UniversityDepartment of Surgical Oncology, Ludwik Rydygier?ˉs Collegium Medicum UMK3P Medicine Lab, Medical University of Gdansk3P Medicine Lab, Medical University of GdanskFaculty of Pharmacy, Medical University of Gdansk||3P Medicine Lab, Medical University of GdanskDepartment of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDepartment of Tumor Pathology, Prof. F. Lukaszczyk Oncology Center||Chair of Clinical Pathomorphology, Collegium Medicum UMK
肿瘤学基础医学分子生物学
Buckley Patrick G.,Kostecka Anna,Nowikiewicz Tomasz,Olszewski Pawe?,Mair Theresa,Gucwa Magdalena,Hartman Johan,Zegarski Wojciech,Tiemann-Boege Irene,Dumanski Jan P.,Jankowski Micha?,Skokowski Jaros?aw,Koczkowska Magdalena,Madanecki Piotr,P?ksa Rafa?,Heinzl Monika,Salazar Renato,?rutek Ewa,Andreou Maria,Horbacz Monika,Piotrowski Arkadiusz,Davies Hanna,Szylberg ?ukasz.High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing[EB/OL].(2025-03-28)[2025-05-15].https://www.medrxiv.org/content/10.1101/2021.09.27.21263863.点此复制
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