High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing.

Autor: Kostecka A; Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland. anna.kostecka@gumed.edu.pl.; 3P Medicine Lab, Medical University of Gdansk, Gdansk, Poland. anna.kostecka@gumed.edu.pl., Nowikiewicz T; Department of Surgical Oncology, Ludwik Rydygier's Collegium Medicum UMK, Bydgoszcz, Poland. tomasz.nowikiewicz@gmail.com.; Department of Breast Cancer and Reconstructive Surgery, Prof. F. Lukaszczyk Oncology Center, Bydgoszcz, Poland. tomasz.nowikiewicz@gmail.com., Olszewski P; 3P Medicine Lab, Medical University of Gdansk, Gdansk, Poland., Koczkowska M; Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland.; 3P Medicine Lab, Medical University of Gdansk, Gdansk, Poland., Horbacz M; 3P Medicine Lab, Medical University of Gdansk, Gdansk, Poland., Heinzl M; Institute of Biophysics, Johannes Kepler University, Linz, Austria., Andreou M; 3P Medicine Lab, Medical University of Gdansk, Gdansk, Poland., Salazar R; Institute of Biophysics, Johannes Kepler University, Linz, Austria., Mair T; Institute of Biophysics, Johannes Kepler University, Linz, Austria., Madanecki P; Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland., Gucwa M; Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland., Davies H; Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Skokowski J; Department of Surgical Oncology, Medical University of Gdansk, Gdansk, Poland., Buckley PG; Genuity Science Genomics Centre, Dublin, Ireland., Pęksa R; Department of Patomorphology, Medical University of Gdansk, Gdansk, Poland., Śrutek E; Department of Surgical Oncology, Ludwik Rydygier's Collegium Medicum UMK, Bydgoszcz, Poland., Szylberg Ł; Department of Tumor Pathology, Prof. F. Lukaszczyk Oncology Center, Bydgoszcz, Poland.; Department of Perinatology, Gynaecology and Gynaecologic, Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland., Hartman J; Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.; Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.; MedTech Labs, Bioclinicum, Karolinska University Hospital, Stockholm, Sweden., Jankowski M; Department of Surgical Oncology, Ludwik Rydygier's Collegium Medicum UMK, Bydgoszcz, Poland., Zegarski W; Department of Surgical Oncology, Ludwik Rydygier's Collegium Medicum UMK, Bydgoszcz, Poland., Tiemann-Boege I; Institute of Biophysics, Johannes Kepler University, Linz, Austria., Dumanski JP; 3P Medicine Lab, Medical University of Gdansk, Gdansk, Poland.; Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Piotrowski A; Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland. arkadiusz.piotrowski@gumed.edu.pl.; 3P Medicine Lab, Medical University of Gdansk, Gdansk, Poland. arkadiusz.piotrowski@gumed.edu.pl.
Jazyk: angličtina
Zdroj: NPJ breast cancer [NPJ Breast Cancer] 2022 Jun 29; Vol. 8 (1), pp. 76. Date of Electronic Publication: 2022 Jun 29.
DOI: 10.1038/s41523-022-00443-9
Abstrakt: 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. Targeted resequencing of 542 cancer-associated genes revealed subclonal 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 - 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 subclonal (in 10 -2 -10 -4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumorous mammary gland tissue of breast-conserving surgery patients.
(© 2022. The Author(s).)
Databáze: MEDLINE
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