Fibroadenomas (FAs) are the most common fibroepithelial lesions and the most common benign tumors of the breast in women of reproductive age. Although MED12 mutations, an overwhelming majority of all mutations, and some other gene mutations have been found in FAs, the genomic landscapes of FAs are still not completely clear and the genomic mutation spectrums of FAs in Chinese population remains unknown. Here, by performing whole exome sequencing of 12 FAs and the corresponding normal breast tissues in Chinese Han population, we observed the somatic and germline landscapes of genetic alterations. We identified 16 recurrently mutated genes with 37 nonsynonymous or frameshift somatic mutations and 27 recurrent somatic copy number variants (CNVs). In these mutated genes, MED12 was the most common in FAs, harboring 6 nonsynonymous/frameshift somatic mutations and 1 CNV. In addition, 6 germline mutations of tumor susceptibility genes in 5 FAs were identified and the tumor mutational burden of the 5 FAs was significantly higher than the other 7 FAs without germline mutations. This study provides genomic mutation spectrums of FAs in Chinese population and expand the genetic spectrum of FAs.
Keywords: MED12; copy number variation; fibroadenoma; germline mutation; somatic mutation; tumor mutational burden.
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.