Abstract
BackgroundNext-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.MethodsTriplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.ResultsSuccessful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.ConclusionsThe QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.
Highlights
Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor
The microscopic evaluation of these cases found that normal breast tissue, sufficient (20% or more tumor content) primary breast cancer tissue, and tissue from at least one relapse site were available for 35 patients
DNA quality and QIAseq human breast Cancer panel The data for DNA quality are shown in Supplementary Table 2
Summary
Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. Studies using next-generation sequencing (NGS) have demonstrated remodeling of genes in metastatic cancer compared with the primary tumor from the same individual, possibly as a result of subclonal diversification or mutational. In 2016, Muller et al reported that 45% (10/22) of metastatic breast cancers contained molecular targets for currently available therapies, including for offlabel use [13]. The aim of the present study was to perform breast cancer-targeted NGS to compare gene mutations and copy number variations (CNVs) in samples of primary breast cancer and recurrent/metastatic lesions from the same individuals. This study aimed to clarify the practical possibility of breast cancer-targeted NGS and improve understanding of subclonal diversification or mutational evolution of metastatic breast cancers
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