Clinical utility of next-generation sequencing-based ctDNA testing for common and novel ALK fusions

Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) can detect ALK fusions, though data on clinical utility of this technology in the real world is limited. Materials and Methods: Patients with lung cancer without known oncogenic drivers or who had acquired resistance to therapy (n = 736) underwent prospective plasma ctDNA NGS. A subset of this cohort (n = 497) also had tissue NGS. We evaluated ALK fusion detection, turnaround time (TAT), plasma and tissue concordance, matching to therapy, and treatment response. Results: ctDNA identified an ALK fusion in 21 patients (3%) with a variety of breakpoints and fusion partners, including EML4, CLTC, and PON1, a novel ALK fusion partner. TAT for ctDNA NGS was shorter than tissue NGS (10 vs. 20 days; p < 0.001). Among ALK fusions identified by ctDNA, 93% (13/14, 95% CI 66%–99%) were concordant with tissue evaluation. Among ALK fusions detected by tissue NGS, 54% (13/24, 95% CI 33%–74%) were concordant with p..... READ ARTICLE

Lung Cancer
DOI:10.1016/j.lungcan.2021.06.018

Authors: Sebastian Mondaca, Emily S. Lebow, Azadeh Namakydoust, Pedram Razav, Jorge S. Reis-Filho, Ronglai Shen, Michael Offin, Hai-Yan Tu, Yonina Murciano-Goroff, Chongrui Xu, Alex Makhnin, Andres Martinez, Nick Pavlakis, Stephen Clarke, Malinda Itchins, Adrian Lee, Andreas Rimner, Daniel Gomez and Bob T. Li

Pre-Clinical, group2Kirk SmithNovember 29, 2021Liquid biopsy, Circulating tumor DNA, Next generation sequencing, ALK fusion

Attenuated isolated 3’ signal: A highly challenging therapy relevant ALK FISH pattern in NSCLC

Objectives: ... Our aim was to examine a unique atypical ALK FISH pattern, revealed during a systematic large-scale monitoring, which carries the great risk of misinterpretation, hence may result in loss of patients eligible for targeted therapy... Conclusion: Approximately 5% of the 59 ALK positive cases exhibited atypical attenuated isolated 3′ signal pattern. The immunohistochemistry and AMP-NGS examinations helped to clarify the presence of oncoprotein and the fusion gene, respectively. Our results emphasize the importance of extensive exploration of the genetic background of any unexpected FISH finding to avoid false diagnosis. This enables clinicians to indicate the adequate therapy with higher efficiency for patients suffering from NSCLC. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.03.007

Authors: Gábor Smuk, Gábor Pajor, Károly Szuhai, Hans Morreau, Ildikó Kocsmár, Éva Kocsmár, László Pajor, Béla Kajtár, Veronika Sárosi, Gábor Lotz, Tamás Tornóczky

Review PaperKirk SmithMay 1, 2020Non-small cell lung cancer, Anaplastic lymphoma kinase, Fluorescence insitu hybridization, Next generation sequencing, Anchored multiplex PCR, Downstream deletion