Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-020-07432-w |
| _version_ | 1811306126236450816 |
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| author | Toshiaki Akahane Naoki Kanomata Oi Harada Tetsumasa Yamashita Junichi Kurebayashi Akihide Tanimoto Takuya Moriya |
| author_facet | Toshiaki Akahane Naoki Kanomata Oi Harada Tetsumasa Yamashita Junichi Kurebayashi Akihide Tanimoto Takuya Moriya |
| author_sort | Toshiaki Akahane |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T08:38:49Z |
| format | Article |
| id | doaj.art-4a94328c201145c397ad92c2dc7126b0 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T08:38:49Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-4a94328c201145c397ad92c2dc7126b02022-12-22T02:53:58ZengBMCBMC Cancer1471-24072020-10-012011910.1186/s12885-020-07432-wTargeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesionsToshiaki Akahane0Naoki Kanomata1Oi Harada2Tetsumasa Yamashita3Junichi Kurebayashi4Akihide Tanimoto5Takuya Moriya6Department of Pathology, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Pathology, St. Luke’s International HospitalDepartment of Pathology, Hokuto HospitalDepartment of Breast and Thyroid Surgery, Kawasaki Medical SchoolDepartment of Breast and Thyroid Surgery, Kawasaki Medical SchoolDepartment of Pathology, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Pathology, Kawasaki Medical SchoolAbstract 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.http://link.springer.com/article/10.1186/s12885-020-07432-wBreast cancerMetastasisRecurrenceNext-generation sequencing |
| spellingShingle | Toshiaki Akahane Naoki Kanomata Oi Harada Tetsumasa Yamashita Junichi Kurebayashi Akihide Tanimoto Takuya Moriya Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions BMC Cancer Breast cancer Metastasis Recurrence Next-generation sequencing |
| title | Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions |
| title_full | Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions |
| title_fullStr | Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions |
| title_full_unstemmed | Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions |
| title_short | Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions |
| title_sort | targeted next generation sequencing assays using triplet samples of normal breast tissue primary breast cancer and recurrent metastatic lesions |
| topic | Breast cancer Metastasis Recurrence Next-generation sequencing |
| url | http://link.springer.com/article/10.1186/s12885-020-07432-w |
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