Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients

König, Katharina; Peifer, Martin; Fassunke, Jana; Ihle, Michaela A.; Künstlinger, Helen; Heydt, Carina; Stamm, Katrin; Ueckeroth, Frank; Vollbrecht, Claudia; Bos, Marc; Gardizi, Masyar; Scheffler, Matthias; Nogová, Lucia; Leenders, Frauke; Albus, Kerstin; Meder, Lydia; Becker, Kerstin; Florin, Alexandra; Rommerscheidt-Fuss, Ursula; Altmüller, Janine; Kloth, Michael; Nürnberg, Peter; Henkel, Thomas; Bikár, Sven-Ernö; Sos, Martin L.; Geese, William J.; Strauss, Lewis C.; Ko, Yon‐Dschun; Gerigk, Ulrich; Odenthal, Margarete; Zander, Thomas; Wolf, Jürgen; Merkelbach‐Bruse, Sabine; Buettner, Reinhard; Heukamp, Lukas C.

doi:10.1097/jto.0000000000000570

Cited by 88 publications

(63 citation statements)

References 49 publications

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“…The initial study concluded that gain of functions mutations in DDR2 are oncogenic and provided the first targetable mutations in lung SCC [116] and hence caused much excitement in the field. However, the study did not address the contribution of wild-type DDR2 to oncogenesis, and while several more recent studies have confirmed the occurrence of DDR2 mutations in different patient populations [122][123][124], it is far from clear whether the mutations are indeed oncogenic and their roles in lung SCC cell signalling are undefined [125]. Notably, in other studies, some of the 'oncogenic' DDR2 mutants either seemed to play tumour suppressive functions [101], or did not contribute to cell proliferation in lung SCC cell lines [126].…”

Section: Ddrs and Cancermentioning

confidence: 99%

Extracellular matrix component signaling in cancer

Multhaupt

Leitinger

Gullberg

et al. 2016

Advanced Drug Delivery Reviews

154

109

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Section: Ddrs and Cancermentioning

confidence: 99%

Extracellular matrix component signaling in cancer

Multhaupt

Leitinger

Gullberg

et al. 2016

Advanced Drug Delivery Reviews

154

109

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“…In particular, predictive genetic alteration testing is relevant as the molecular complexity of lung cancer is evolving [10]. Targeted PCR-based sequencing can be performed on > 80% of the routine EBUS-TBNA specimens, but only a limited number of studies did evaluate next-generation sequencing (NGS) assays performed on fine needle aspirations [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

A Randomized Clinical Trial of Flex 19G Needles versus 22G Needles for Endobronchial Ultrasonography in Suspected Lung Cancer

et al. 2018

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Background: A flexible 19-gauge (Flex 19G) needle has been developed for endobronchial ultrasonography. Objectives: We aimed to evaluate quantitative and qualitative specimen characteristics of Flex 19G in a randomized controlled setting for patients with suspected lung cancer. Methods: We undertook a single-center, randomized, controlled trial. A computer-generated randomization assigned all enrolled patients 1: 1 to undergo endobronchial ultrasonography using a Flex 19G or a 22-gauge (22G) needle for lymph node tissue sampling. Pathologists were blinded to the group assignment. The primary end point was histological tissue core procurement. The secondary end points were diagnostic yield, specimen bloodiness and overall quality, tissue surface area and performance for next-generation sequencing (NGS), and procedure-related complications. Results: Between June 2016 and February 2017, we randomly allocated a total of 78 patients: 39 patients to Flex 19G and 39 patients to 22G. No superiority in tissue core procurement was observed for Flex 19G compared to 22G (67 vs. 72%, p = 0.81). No significant difference was observed in diagnostic yield and overall specimen quality, but transbronchial needle aspiration specimens by Flex 19G were bloodier and had a larger tissue surface area. NGS was successful for clinically relevant genes in 96% and for all 26 genes tested in 81% of the samples. There was no difference in clinically relevant complications. Conclusions: No superiority is observed for Flex 19G in histological tissue core procurement rate. The Flex 19G needle could be considered when a larger tissue surface is of special interest.

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“…Samples were microdissected, tumor DNA was extracted, and conventional Sanger sequencing of EGFR exons 18-21 was performed, using routine diagnostic protocols with external quality assessment [33]. Massive parallel sequencing was performed in Cologne on the Illumina® platform (Illumina, Inc., San Diego, CA, USA), using TrueSeq® Amplicon lung panels #3 and #4 (Illumina) [34]. These panels cover most somatic mutations presently known in NSCLC (table 1).…”

Section: Methodsmentioning

confidence: 99%

Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy

Gautschi

Stadelmann²,

Aebersold-Keller³

et al. 2015

Oncol Res Treat

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Background: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned. Patients and Methods: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR. Results: Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC. Conclusion: Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.

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Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients

Abstract: Overall, our data demonstrate the utility of systematic sequencing analysis in a clinical routine setting and highlight the dramatic impact of such an approach on the availability of therapeutic strategies for the targeted treatment of individual cancer patients.

Cited by 88 publications

References 49 publications

Extracellular matrix component signaling in cancer

Extracellular matrix component signaling in cancer

A Randomized Clinical Trial of Flex 19G Needles versus 22G Needles for Endobronchial Ultrasonography in Suspected Lung Cancer

Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy

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