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

被引：13

作者：

Kostecka, Anna ^{[1
,2
]}

Nowikiewicz, Tomasz ^{[3
,4
]}

Olszewski, Pawel ^{[2
]}

Koczkowska, Magdalena ^{[1
,2
]}

Horbacz, Monika ^{[2
]}

Heinzl, Monika ^{[5
]}

Andreou, Maria ^{[2
]}

Salazar, Renato ^{[5
]}

Mair, Theresa ^{[5
]}

Madanecki, Piotr ^{[1
]}

Gucwa, Magdalena ^{[1
]}

Davies, Hanna ^{[6
]}

Skokowski, Jaroslaw ^{[7
]}

Buckley, Patrick G. ^{[8
]}

Peksa, Rafal ^{[9
]}

Srutek, Ewa ^{[3
]}

Szylberg, Lukasz ^{[10
,11
]}

Hartman, Johan ^{[12
,13
,14
]}

Jankowski, Michal ^{[3
]}

Zegarski, Wojciech ^{[3
]}

Tiemann-Boege, Irene ^{[5
]}

Dumanski, Jan P. ^{[2
,6
]}

Piotrowski, Arkadiusz ^{[1
,2
]}

机构：

[1] Med Univ Gdansk, Fac Pharm, Gdansk, Poland

[2] Med Univ Gdansk, 3P Med Lab, Gdansk, Poland

[3] Ludwik Rydygiers Coll Med UMK, Dept Surg Oncol, Bydgoszcz, Poland

[4] Prof F Lukaszczyk Oncol Ctr, Dept Breast Canc & Reconstruct Surg, Bydgoszcz, Poland

[5] Johannes Kepler Univ Linz, Inst Biophys, Linz, Austria

[6] Uppsala Univ, Dept Immunol Genet & Pathol & Sci Life Lab, Uppsala, Sweden

[7] Med Univ Gdansk, Dept Surg Oncol, Gdansk, Poland

[8] Genu Sci Genom Ctr, Dublin, Ireland

[9] Med Univ Gdansk, Dept Patomorphol, Gdansk, Poland

[10] Prof F Lukaszczyk Oncol Ctr, Dept Tumor Pathol, Bydgoszcz, Poland

[11] Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, Dept Perinatol Gynaecol & Gynaecol Oncol, Bydgoszcz, Poland

[12] Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden

[13] Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden

[14] Karolinska Univ Hosp, MedTech Labs, Bioclinicum, Stockholm, Sweden

来源：

NPJ BREAST CANCER | 2022年 / 8卷 / 01期

关键词：

GENE-EXPRESSION PATTERNS; HIGH-RISK; MUTATIONS; LANDSCAPE; NUMBER; WOMEN;

D O I：

10.1038/s41523-022-00443-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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, R81, NCOR1, MED12, CBFB, T8X3, and TSHR in the normal mammary gland at considerable allelic frequencies (9 x 10(-2) - 5.2 x 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.

引用

页数：10

共 16 条

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