Concordance between comprehensive cancer genome profiling in plasma and matched tumor specimens.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23146-e23146
Author(s):  
Roopika Menon ◽  
Judith N Müller ◽  
Markus Falk ◽  
Sotirios Lakis ◽  
Erika Mariotti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Mutational Analysis ◽  
Massively Parallel Sequencing ◽  
Point Mutations ◽  
Liquid Biopsies ◽  
Genomic Alterations ◽  
Pathology Laboratory ◽  
Tissue Samples ◽  
Routine Diagnostics

e23146 Background: The importance and clinical use of liquid biopsies to identify somatic, targetable alterations in the plasma of cancer patients is steadily increasing. However, their concordance with alterations identified in cancer specimens tested in routine diagnostics is not being monitored. In a cohort of non-squamous cell lung cancer patients, our aim was to systematically compare alterations found by a massively parallel sequencing liquid biopsy assay covering 39 cancer related genes (NEOliquid) with alterations identified by routine diagnostics in a certified central pathology laboratory. Methods: Routine Diagnostics: DNA mutational analysis was performed using cobas or Sanger-Sequencing. Rearrangements were identified using immunohistochemistry or FISH. NEOliquid assay: Cell-free DNA from plasma was subjected to hybrid-capture based next-generation sequencing to detect point mutations, small insertions and deletions, copy number alterations and genomic translocations in 39 clinically relevant genes in a single assay. To evaluate and compare the performance of liquid biopsies, we applied the NEOliquid tests on blood samples of 82 non-squamous NSCLC patients and correlated them with results of routine diagnostics of matched tissue samples. Results: Routine diagnostics for lung cancer related oncogenes (EGFR, ALK, ROS1, KRAS, BRAF) identified a total of 50 somatic alterations of which 37 were point mutations, 11 InDels and 2 gene fusions. NEOliquid analysis of the corresponding plasma sample revealed a total of 34 alterations, including 21 targetable driver alterations. Overall, the concordance of mutation calls between routine diagnostic testing and NEOliquid was 97.6%, with a sensitivity of > 70% and a specificity of 100%. Importantly, NEOliquid identified additional clinically relevant genomic alterations, not covered by routine testing. Conclusions: We have shown high concordance of genomic alterations identified from liquid biopsies and tumor tissue specimens. The excellent specificity of actionable alterations identified by NEOliquid offers analytical performance for routine diagnostic use.

scholarly journals High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations

2021 ◽  
Vol 10 (3) ◽  
pp. 1512-1524
Author(s):  
Yiwei Liu ◽  
Wanying Wang ◽  
Fengying Wu ◽  
Guanghui Gao ◽  
Jian Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Genomic Alterations ◽  
Lung Cancer Patients

Cancer gene profile of metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1015-1015 ◽  
Author(s):  
Funda Meric-Bernstam ◽  
Garrett Frampton ◽  
Jaime Ferrer-Lozano ◽  
Roman Yelensky ◽  
Gary A. Palmer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Point Mutations ◽  
Metastatic Breast ◽  
Genomic Alteration ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Primary Tumors ◽  
Recurrent Tumors

1015 Background: There is great interest in using genomic information to guide therapy selection in cancer patients. The aim of this study was to determine the spectrum of genomic alterations identified in MBC patients, and evaluate the concordance of alterations between primary and recurrent tumors. Methods: We performed comprehensive profiling on formalin-fixed paraffin embedded samples from 42 patients with MBC using a targeted next generation sequencing (NGS) assay in a CLIA laboratory (Foundation Medicine). Genomic libraries were captured for 3,230 exons in 182 cancer related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to an average depth of 390X with 99% of bases covered >100X. In total 30 primary and 37 recurrent tumors were profiled, including 3 separate recurrences in 1 patient and matched primary-recurrences in 22 patients. Point mutations, indels, copy number alterations and rearrangements were assessed. Alterations that are targetable with established or investigational therapeutics were considered “actionable”. Results: At least 1 genomic alteration was identified in all but 2 breast samples (both primary tumors). Point mutations were identified in several cancer-related genes including PIK3CA, TP53, PTEN, CDH1, ARID1A, AKT1, NF1, FBXW7 and FGFR3. Amplification was observed in HER2; 11 of 12 HER2 IHC positive samples were found to have HER2 gains by NGS; in addition, a HER2 gain was identified by NGS in a HER2- (1+ IHC) sample. Amplification of PIK3CA, IGF1R, FGFR2, AKT2, MDM2, and MCL1 plus a CDKN2A homozygous deletion were also identified. While the majority of known driver alterations (85%) were concordant in the matched pairs of primary and recurrent tumors, in 11 of 22 sets there was at least 1 discordant driver alteration, and these included both gains and losses of potential therapeutic targets. Overall 32 of 42 patients (76%) had an actionable genomic alteration. Conclusions: Genomic profiling of breast cancer samples reveals genomic alterations in most metastatic breast cancer patients. Over three quarters of patients have actionable findings, suggesting that genomic profiling may assist in individualized pathway-directed therapy.

scholarly journals Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations

2020 ◽  
Author(s):  
Yuichiro Takeda ◽  
Go Naka ◽  
Yoh Yamaguchi ◽  
Masao Hashimoto ◽  
Manabu Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Liquid Biopsies ◽  
Lung Cancer Patients ◽  
Epidermal Growth ◽  
Egfr Tki ◽  
Egfr Tkis

Abstract Background: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy. Moreover, limited information is available regarding genetic diagnostic approaches after the treatment of EGFR-TKI–naïve patients. This study investigated the clinical characteristics of EGFR -mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs, as well as the advantages of rebiopsy and liquid biopsy for these patients. Methods: The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single-plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy. Results: From April 2016 through May 2019, 113 patients were found to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among whom 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue biopsies and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had a new lesion, and were administered gefitinib as first-line therapy, they were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with coexisting original mutations, brain metastases, tumor enlargement by ≥ 12 mm, or metastases at minor sites. Conclusion: Among patients with positive factors associated with the T790M mutation, repeated tissue or liquid biopsies are useful to maximize the detection rate of the T790M substitution. Furthermore, these biopsies need to be repeated numerous times in order to reduce “detection overlook” among such patients.

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