Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions
| Autor: | Takuya Moriya, Toshiaki Akahane, Tetsumasa Yamashita, Oi Harada, Junichi Kurebayashi, Akihide Tanimoto, Naoki Kanomata |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Cancer Research DNA Copy Number Variations Class I Phosphatidylinositol 3-Kinases Receptor ErbB-2 Breast Neoplasms lcsh:RC254-282 Metastasis 03 medical and health sciences 0302 clinical medicine Germline mutation Breast cancer Recurrence Genetics Medicine Humans Genetic Predisposition to Disease Neoplasm Metastasis EP300 skin and connective tissue diseases Germ-Line Mutation Aged business.industry Cancer High-Throughput Nucleotide Sequencing Genomics Middle Aged medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Metastatic breast cancer Primary tumor Neoplasm Proteins 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Cancer research Next-generation sequencing Female Neoplasm Recurrence Local business |
| Zdroj: | BMC Cancer, Vol 20, Iss 1, Pp 1-9 (2020) |
| Popis: | Background Next-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. Methods Triplet 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. Results Successful 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. Conclusions The 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. |
| Databáze: | OpenAIRE |
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