Rapid detection of genetic mutations in individual breast cancer patients by next-generation DNA sequencing

Liu, Suqin; Wang, Hongjiang; Zhang, Lizhi; Tang, Chuanning; Jones, Lindsey; Ye, Hua; Li-ying, Ban; Wang, Aman; Liu, Zhiyuan; Feng, Li; Zhang, Dandan; Sun, Hong; Dong, Haichao; Zhang, Guangchun; Dong, Zhishou; Guo, Baishuai; Yan, He; Yan, Chaowei; Wang, Lu; Su, Ziyi; Li, Yangyang; Huang, Xue F.; Chen, Si-Yi; Zhou, Tao

doi:10.1186/s40246-015-0024-4

Cited by 36 publications

(23 citation statements)

References 52 publications

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“…Observed genomic alterations of NECs in our series are comparable with the data from previous studies on NEC. 4,8,9,46,47 The molecular alterations (PIK3CA, TP53, RB1, CCND1) in breast NEC are common in invasive ER þ (luminal) ductal carcinomas of no-special-type suggesting potential relevance of cell cycle (CDK4/6 inhibitors) in isolated cases of this rare cancer. 48,49 There are also ongoing clinical trials with cell cycle inhibitors aimed to treat patients with lung and head/neck cancers harboring CCND1 amplification (trials: NCT03356223 and NCT02785939).…”

Section: Ngs and Archer Fusion Resultsmentioning

confidence: 99%

“…Although FGFR inhibitors have been recently considered as a promising therapeutic option in breast cancer, the preliminary clinical data with FGFR inhibitors have yielded disappointing results. 50 IDH1 (isocitrate dehydrogenase 1) mutations have also been described in breast cancer, including luminal breast cancers, 47 and have been associated with a poor prognosis. 51…”

Section: Ngs and Archer Fusion Resultsmentioning

confidence: 99%

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Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Vranić

Palazzo

Sanati

et al. 2019

Clinical Breast Cancer

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Neuroendocrine breast cancer lacks specific therapy, but similar common neuroendocrine carcinomas may offer guidance for therapy development. This study, for the first time, identified several biomarkers for targeted therapy approaches in patients with breast neuroendocrine carcinoma. Introduction: Neuroendocrine carcinoma (NEC) of the breast is a rare, special type of breast cancer, reportedly constituting 2% to 5% of all breast cancers. Although breast NEC does not have a specific targeted therapy, several new targeted therapies based on specific biomarkers were recently investigated in the NEC of lung and in other types of breast carcinoma, which may provide guidance to their feasibility in breast NEC. Materials and Methods: Twenty breast NECs were profiled for biomarkers of therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), histone deacetylase (H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 gene fusions) targeted inhibitors, alkylating agents (MGMT), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays. Results: Predictive expression of TROP-2, FOLR1, and H3K36Me3 were detected in different subsets of tumors and may pave the way for development of novel targeted therapies in some patients with breast NECs. There was no evidence of DLL3 expression, NTRK gene fusions, or MGMT hypermethylation. No biomarkers predictive of immune checkpoint inhibitor efficacy (programmed death-ligand 1 expression, tumor mutational burden, microsatellite instability) were identified. FGFR and CCND1 gene amplifications were detected in isolated cases. Conclusions: This study identified several potential targets for novel therapies in breast NEC, including farletuzumab and mirvetuximab soravtansine (FOLR1), sacituzumab govitecan (TROP-2), and HDAC inhibitors (H3K36Me3). In some cases, CCND1 gene amplification may indicate the usefulness of investigational therapies. The reported results should serve as an early indication of potential clinical relevance in selected patients with breast NEC.

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Section: Ngs and Archer Fusion Resultsmentioning

confidence: 99%

Section: Ngs and Archer Fusion Resultsmentioning

confidence: 99%

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Vranić

Palazzo

Sanati

et al. 2019

Clinical Breast Cancer

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“…The next-generation sequencing Ion Personal Genome Machine (PGM) is capable of screening for mutations in multiple genes simultaneously21, which may be useful in the clinical characterization of plasma ctDNA from lung cancer patients. Therefore, the aim of this prospective study was to evaluate the feasibility of utilizing a targeted DNA sequencing approach with the Ion PGM and AmpliSeq Cancer Panel to detect mutations in 50 cancer-related genes in matched plasma ctDNA and tumor DNA (tDNA) samples from 58 early-stage NSCLC patients.…”

mentioning

confidence: 99%

Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

Chen

Feng²,

Yang

et al. 2016

Sci Rep

Self Cite

104

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Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC.

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“…There was a previous report on single-gene mutation analysis of CTCs and WBCs (25), and another study performed cancer panel analysis of CTCs without WBCs as controls (26). However, to the best of our knowledge, the present study is the first attempt at a CCP using CTCs in conjunction with WBCs.…”

Section: Discussionmentioning

confidence: 84%

Cancer panel analysis of circulating tumor cells in patients with breast cancer

Lee¹,

Lee²,

Choi³

et al. 2018

Oncol Lett

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Liquid biopsy using circulating tumor cells (CTCs) is a noninvasive and repeatable procedure, and is therefore useful for molecular assays. However, the rarity of CTCs remains a challenge. To overcome this issue, our group developed a novel technology for the isolation of CTCs on the basis of cell size difference. The present study isolated CTCs from patients with breast cancer using this method, and then used these cells for cancer gene panel analysis. Blood samples from eight patients with breast cancer were collected, and CTCs were enriched using size-based filtration. Enriched CTCs were counted using immunofluorescent staining with an epithelial cell adhesion molecule (EpCAM) and CD45 antibodies. CTC genomic DNA was extracted, amplified, and screened for mutations in 400 genes using the Ion AmpliSeq Comprehensive Cancer Panel. White blood cells (WBCs) from the same patient served as a negative control, and mutations in CTCs and WBCs were compared. EpCAM cells were detected in seven out of eight patients, and the average number of EpCAM cells was 8.6. The average amount of amplified DNA was 32.7 µg, and the percentage of reads mapped to any targeted region relative to all reads mapped to the reference was 98.6%. The detection rate of CTC-specific mutations was 62.5%. The CTC-specific mutations were enhancer of zeste polycomb repressive complex 2 subunit, notch 1, AT-rich interaction domain 1A, serine/threonine kinase 11, fms related tyrosine kinase 3, MYCN proto-oncogene, bHLH transcription factor, APC, WNT signaling pathway regulator, and phosphatase and tensin homolog. The technique used by the present study was demonstrated to be effective at isolating CTCs at a sufficiently high purity for genomic analysis, and supported the use of comprehensive cancer panel analysis as a potential application for precision medicine.

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Rapid detection of genetic mutations in individual breast cancer patients by next-generation DNA sequencing

Cited by 36 publications

References 52 publications

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

Cancer panel analysis of circulating tumor cells in patients with breast cancer

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