P59.02 Profile of Next-Generation Sequencing (NGS) on MET exon 14 Skipping Mutation and MET Amplification in Lung Cancer: A Calibration Project in China

2021 ◽  
Vol 16 (10) ◽  
pp. S1146-S1147
Author(s):  
W. Wu ◽  
C. Wu ◽  
Y. Liu ◽  
Z. Zhang ◽  
Z. Liang
2019 ◽  
Vol 6 (12) ◽  
pp. 327-332
Author(s):  
Cem Mirili ◽  
Çiğdem Kahraman ◽  
Ali Yılmaz ◽  
Mehmet Bilici ◽  
Salim Başol Tekin ◽  
...  

Objective:  In Lung cancer (LC), which is one of the most deadly cancers, longer survival has been achieved with targeted agents. For this reason, it is important to find the patients who are suitable for targeted therapies. Next-generation sequencing (NGS) is a method that allows multiple genetic variants to be detected simultaneously by performing massive parallel DNA sequencing at the same time. We wanted to reveal the clinical effects and benefits of genetic variant analysis with NGS for our patients. Material and Methods: Patients with stage 4 non-squamous and not otherwise specified (NOS) Non-small cell LC who underwent genetic variant analysis with NGS were included in the study, retrospectively. Results: Total of the 51 patients, 41 (80.4%) were male and the median age was 64 (35-85) years. According to TNM, 21 (41.2%) patients were stage 4A, 30 (58.8%) patients were stage 4B and 39 (76.5%) patients had adenocarcinoma and 12 (23.5%) had NOS histology. NGS analyzes were performed in median 14 days (8-43) and determined 24 pathogenic variants in 17 (%25) patients: 9EGFR (%17,6), 6PIKC3A (%11,7), 5KRAS (%9,8), 2PTEN (%3,9), 1BRAF (%1,9), 1MET (%1,6) (7 of them concomitantly). Cytotoxic chemotherapy was recommended in 41, anti-EGFR agents in 8 (afatinib in 4, erlotinib in 4 patients) patients and anti-BRAF+MEK inhibitor agent (dabrafenib+trametinib) in 1 patient. Conclusion: With the NGS, in just two weeks, both target and resistance genetic variants of our patients were detected at the same time and individualized treatments were applied. In this way, both time and cost were saved.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7600-7600
Author(s):  
Maria Catherine Pietanza ◽  
Anna M. Varghese ◽  
Helen H. Won ◽  
Lu Wang ◽  
Natasha Rekhtman ◽  
...  

7600 Background: Oncogenic events in adenocarcinoma and squamous cell cancers of the lung are well described. In contrast, the repertoire of possible molecular targets in SCLC is still unclear. Recent studies using next generation sequencing on rare resected SCLC specimens have provided insights into the molecular heterogeneity of this disease. Comprehensive, prospective molecular profiling of patients with SCLC using the small biopsy specimens available in clinical practice has not been performed. Methods: Utilizing an IRB-approved protocol to prospectively test SCLC tumors (Small Cell Lung Cancer Mutation Analysis Program, “SC-MAP”), these biopsies are evaluated by: FISH for FGFR1 and MET amplification; immunohistochemistry for MGMT and PTEN loss; point mutation genotyping with Sequenom for PIK3CA (and others); and next-generation sequencing with our MSK-IMPACT assay (Integrated Mutation Profiling of Actionable Cancer Targets). MSK-IMPACT uses exon capture followed by massively parallel sequencing to profile all protein-coding exons and select introns of 279 cancer-associated genes, enabling the identification of mutations, indels, and copy number alterations of these genes. We tested the feasibility of this approach in a series of patients with SCLC. We performed next generation sequencing with MSK-IMPACT, with findings confirmed by FISH. Results: We identified 11 patients with SCLC with FFPE samples available from both matched normal tissue and small tumor biopsies, including 3 core biopsies and 8 fine needle aspirations. 9/11 patients had adequate tissue for MSK-IMPACT, which revealed recurrent mutations in Rb1 (N=7) and p53 (N=7), FGFR1 amplification (N=2), and MET amplification (N=1), using as little as 15 nanograms of DNA. FGFR1 and MET amplification were confirmed by FISH testing. We have initiated this prospective SC-MAP program for our patients with SCLC. Conclusions: Comprehensive molecular evaluation of SCLC is feasible on clinically available, small samples. Such analyses will allow us to characterize the molecular diversity of this disease and identify patients who will be candidates for targeted therapies.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16061-e16061
Author(s):  
Ivan De Dios ◽  
Wanlong Ma ◽  
Spiraggelos Antzoulatos ◽  
Jeffrey Estella ◽  
Maher Albitar

e16061 Background: Fibroblast Growth Factor Receptors (FGFR1-4) abnormalities (fusion, amplification and mutations) are common in urothelial, breast and endometrial cancers. However, FGFR1-4 have been shown to play a major role in cell proliferation, differentiation, and apoptosis in other types of cancers including colorectal (CRC) and lung cancers. We explored the value of using DNA and RNA next generation sequencing (NGS) in determining the presence of abnormalities in FGFR1-4 in various types of cancer. Methods: Using targeted panel and next generation sequencing (NGS), we analyzed DNA sequencing data (434 genes) in 438 Solid tumors and RNA data (1408 genes) in 160 lung cancers and 53 colorectal cancers (CRC). The expression levels of the CRC and lung cancer were also compared with expression levels of 32 cases of endometrial, urothelial and breast cancers as a group of cancers known to have high incidence. Results: The DNA data showed mutations in 85 samples and CNV in 12 samples. The detected mutations were 18% in FGFR1, 25% in FGFR2, 45% in FGFR3, and 12% in FGFR4. Only 20% of the detected mutations by NGS testing can be detected if the PCR-based FDA-approved kit was used. Analysis of the expression levels of FGFR1-4 mRNA in CRC and lung cancer showed highest expression in FGFR2, followed by FGFR1 then FGFR3. Expression of FGFR4 was the lowest (P < 0.0001). There was no difference between CRC and lung cancer in FGFR1 and FGFR2 mRNA, but FGFR3 was slightly higher in lung cancer as compared with CRC (P = 0.01). FGFR4 was significantly higher in CRC as compared with lung cancer (P < 0.0001). No fusion involving FGFR1-4 was detected in any of the tested CRC or lung cancers. Upon comparing overall expression between CRC/lung cancer with the group of cancers that are known to have high incidence of FGFR1-4 abnormalities (urothelial, breast, and endometrial), FGFR1 and FGFR2 mRNA were significantly lower in CRC/lung cancers (P < 0.0001 and P = 0.0002, respectively), but there was no significant difference in FGFR3. However, significant overlap is noted. In contrast, FGFR4 was significantly higher in CRC (P < 0.0001). Conclusions: This data suggests that while FGFR1-3 genes are overall expressed in CRC and lung, some cases may have significantly high expression of FGFR1-3 and perhaps these cases should be singled out for treatment with FGFR inhibitors. Furthermore, NGS testing for mutations significantly more efficient and can detect significant number of mutations that can be missed if PCR-based testing is used. NGS testing of DNA and RNA is the most appropriate testing for abnormalities in FGFR1-4.


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