Somatic pathogenic variants in the normal mammary gland of sporadic breast cancer patients.

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 (9x10-2 to 5.2x10-1) 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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001008327	This dataset contains .fastq files generated by targeted DNA sequencing of 542 cancer-associated and cadidate genes (52 individuals), and targeted duplex sequencing of PIK3CA and TP53 genes (4 individuals).	HiSeq X Ten NextSeq 550	156
EGAD00010002250	Genotyping array data for normal mammary gland control samples	Illumina	50
EGAD00010002251	Genotyping array data for breast cancer and matched normal mammary gland samples	Illumina	100

Publications	Citations
High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing. Kostecka A, Nowikiewicz T, Olszewski P, Koczkowska M, Horbacz M, Heinzl M, Andreou M, Salazar R, Mair T, Madanecki P, Gucwa M, Davies H, Skokowski J, Buckley PG, Pęksa R, Śrutek E, Szylberg Ł, Hartman J, Jankowski M, Zegarski W, Tiemann-Boege I, Dumanski JP, Piotrowski A. NPJ Breast Cancer 8: 2022 76	6

Publications

Citations

High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing.
Kostecka A, Nowikiewicz T, Olszewski P, Koczkowska M, Horbacz M, Heinzl M, Andreou M, Salazar R, Mair T, Madanecki P, Gucwa M, Davies H, Skokowski J, Buckley PG, Pęksa R, Śrutek E, Szylberg Ł, Hartman J, Jankowski M, Zegarski W, Tiemann-Boege I, Dumanski JP, Piotrowski A. NPJ Breast Cancer 8: 2022 76