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High prevalence of ...
High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing
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- Kostecka, A (author)
- Med Univ Gdansk, Fac Pharm, Gdansk, Poland.;Med Univ Gdansk, 3P Med Lab, Gdansk, Poland.
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- Nowikiewicz, T (author)
- Ludwik Rydygiers Coll Med UMK, Dept Surg Oncol, Bydgoszcz, Poland.;Prof F Lukaszczyk Oncol Ctr, Dept Breast Canc & Reconstruct Surg, Bydgoszcz, Poland.
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- Olszewski, P (author)
- Med Univ Gdansk, 3P Med Lab, Gdansk, Poland.
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- Koczkowska, M (author)
- Med Univ Gdansk, Fac Pharm, Gdansk, Poland.;Med Univ Gdansk, 3P Med Lab, Gdansk, Poland.
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- Horbacz, M (author)
- Med Univ Gdansk, 3P Med Lab, Gdansk, Poland.
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- Heinzl, M (author)
- Johannes Kepler Univ Linz, Inst Biophys, Linz, Austria.
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- Andreou, M (author)
- Med Univ Gdansk, 3P Med Lab, Gdansk, Poland.
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- Salazar, R (author)
- Johannes Kepler Univ Linz, Inst Biophys, Linz, Austria.
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- Mair, T (author)
- Johannes Kepler Univ Linz, Inst Biophys, Linz, Austria.
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- Madanecki, P (author)
- Med Univ Gdansk, Fac Pharm, Gdansk, Poland.
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- Gucwa, M (author)
- Med Univ Gdansk, Fac Pharm, Gdansk, Poland.
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- Davies, Hanna (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Skokowski, J (author)
- Med Univ Gdansk, Dept Surg Oncol, Gdansk, Poland.,Ludwik Rydygiers Coll Med UMK, Dept Surg Oncol, Bydgoszcz, Poland.
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- Buckley, PG (author)
- Genu Sci Genom Ctr, Dublin, Ireland.
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- Peksa, R (author)
- Med Univ Gdansk, Dept Patomorphol, Gdansk, Poland.
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- Srutek, E (author)
- Ludwik Rydygiers Coll Med UMK, Dept Surg Oncol, Bydgoszcz, Poland.
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- Szylberg, L (author)
- Prof F Lukaszczyk Oncol Ctr, Dept Tumor Pathol, Bydgoszcz, Poland.;Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, Dept Perinatol Gynaecol & Gynaecol Oncol, Bydgoszcz, Poland.
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- Hartman, J (author)
- Karolinska Institutet,Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, MedTech Labs, Bioclinicum, Stockholm, Sweden.
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Jankowski, M (author)
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- Zegarski, W (author)
- Ludwik Rydygiers Coll Med UMK, Dept Surg Oncol, Bydgoszcz, Poland.
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- Tiemann-Boege, I (author)
- Johannes Kepler Univ Linz, Inst Biophys, Linz, Austria.
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- Dumanski, Jan P. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Med Univ Gdansk, 3P Med Lab, Gdansk, Poland.
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- Piotrowski, A (author)
- Med Univ Gdansk, Fac Pharm, Gdansk, Poland.;Med Univ Gdansk, 3P Med Lab, Gdansk, Poland.
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Med Univ Gdansk, Fac Pharm, Gdansk, Poland;Med Univ Gdansk, 3P Med Lab, Gdansk, Poland. Ludwik Rydygiers Coll Med UMK, Dept Surg Oncol, Bydgoszcz, Poland.;Prof F Lukaszczyk Oncol Ctr, Dept Breast Canc & Reconstruct Surg, Bydgoszcz, Poland. (creator_code:org_t)
- 2022-06-29
- 2022
- English.
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In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 8:1, s. 76-
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Kostecka, A
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Nowikiewicz, T
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Olszewski, P
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Koczkowska, M
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Horbacz, M
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Heinzl, M
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show more...
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Andreou, M
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Salazar, R
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Mair, T
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Madanecki, P
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Gucwa, M
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Davies, Hanna
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Skokowski, J
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Buckley, PG
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Peksa, R
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Srutek, E
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Szylberg, L
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Hartman, J
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Jankowski, M
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Zegarski, W
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Tiemann-Boege, I
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Dumanski, Jan P.
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Piotrowski, A
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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NPJ breast cance ...
- By the university
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Karolinska Institutet
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Uppsala University