PMID- 30898567 OWN - NLM STAT- MEDLINE DCOM- 20200403 LR - 20200403 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 20 IP - 4 DP - 2019 Jul TI - Next-generation Sequencing for ALK and ROS1 Rearrangement Detection in Patients With Non-small-cell Lung Cancer: Implications of FISH-positive Patterns. PG - e421-e429 LID - S1525-7304(19)30058-0 [pii] LID - 10.1016/j.cllc.2019.02.008 [doi] AB - BACKGROUND: Detection of ALK and ROS1 gene rearrangements in non-small-cell lung cancer is required for directing patient care. Although fluorescence in situ hybridization (FISH) and immunohistochemistry have been established as gold standard methods, next-generation sequencing (NGS) platforms are called to be at least equally successful. Comparison of these methods for translation into daily use is currently under investigation. PATIENTS AND METHODS: Forty non-small-cell lung cancer paraffin-embedded samples with previous ALK (n = 33) and ROS1 (n = 7) FISH results were examined with the Oncomine Focus Assay and tested for ALK and ROS1 immunoreactivity. Clinical implications of concurrent molecular alterations and concordance between methods were evaluated. RESULTS: NGS was successful in 32 (80%) cases: 25 ALK and 7 ROS1. Few concomitant alterations were detected: 1 ALK rearranged case had an ALK p.L1196M-resistant mutation, 4 had CDK4, MYC, and/or ALK amplifications, and 1 ROS1 rearranged case showed a FGFR4 amplification. Comparison between techniques revealed 5 (16%) discordant cases that had lower progression-free survival than concordant cases: 7.6 (95% confidence interval, 2.2-13) versus 19.4 (95% confidence interval, 10.1-28.6). Remarkably, 4 of these cases had isolated 3' signal FISH pattern (P = .026). CONCLUSION: Our data support that the identification of 3' isolated signal FISH pattern in ALK and ROS1 cases might suggest a false-positive result. NGS seems a reliable technique to assess ALK and ROS1 rearrangements, offering the advantage over immunohistochemistry of detecting other molecular alterations with potential therapeutic implications. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Clave, Sergi AU - Clave S AD - Pathology Department, Hospital del Mar, Barcelona, Spain; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain. FAU - Rodon, Natalia AU - Rodon N AD - BIOPAT Biopatologia Molecular, Grup Assistencia, Barcelona, Spain. FAU - Pijuan, Lara AU - Pijuan L AD - Pathology Department, Hospital del Mar, Barcelona, Spain. FAU - Diaz, Olga AU - Diaz O AD - BIOPAT Biopatologia Molecular, Grup Assistencia, Barcelona, Spain. FAU - Lorenzo, Marta AU - Lorenzo M AD - Pathology Department, Hospital del Mar, Barcelona, Spain; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain. FAU - Rocha, Pedro AU - Rocha P AD - Medical Oncology Department, Hospital del Mar, Barcelona, Spain. FAU - Taus, Alvaro AU - Taus A AD - Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain; Medical Oncology Department, Hospital del Mar, Barcelona, Spain. FAU - Blanco, Remei AU - Blanco R AD - Medical Oncology Department, Consorci Sanitari de Terrassa, Terrassa, Spain. FAU - Bosch-Barrera, Joaquim AU - Bosch-Barrera J AD - Medical Oncology Department, Catalan Institute of Oncology, Hospital Dr. Josep Trueta, Girona, Spain. FAU - Reguart, Noemi AU - Reguart N AD - Medical Oncology Department, Hospital Clinic, Barcelona, Spain. FAU - de la Torre, Noelia AU - de la Torre N AD - Pathology Department, Consorci Sanitari de Terrassa, Terrassa, Spain. FAU - Oliveras, Gloria AU - Oliveras G AD - Medical Oncology Department, Catalan Institute of Oncology, Hospital Dr. Josep Trueta, Girona, Spain. FAU - Espinet, Blanca AU - Espinet B AD - Pathology Department, Hospital del Mar, Barcelona, Spain; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain. FAU - Bellosillo, Beatriz AU - Bellosillo B AD - Pathology Department, Hospital del Mar, Barcelona, Spain; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain. FAU - Puig, Xavier AU - Puig X AD - BIOPAT Biopatologia Molecular, Grup Assistencia, Barcelona, Spain. FAU - Arriola, Edurne AU - Arriola E AD - Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain; Medical Oncology Department, Hospital del Mar, Barcelona, Spain. FAU - Salido, Marta AU - Salido M AD - Pathology Department, Hospital del Mar, Barcelona, Spain; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain. Electronic address: msalido@parcdesalutmar.cat. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190226 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Anaplastic Lymphoma Kinase/*genetics MH - Carcinoma, Non-Small-Cell Lung/*diagnosis/genetics/mortality MH - Female MH - Gene Rearrangement MH - High-Throughput Nucleotide Sequencing/*methods MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*diagnosis/genetics/mortality MH - Male MH - Middle Aged MH - Protein-Tyrosine Kinases/*genetics MH - Proto-Oncogene Proteins/*genetics MH - Reproducibility of Results MH - Survival Analysis OTO - NOTNLM OT - Concurrent alterations OT - Fluorescence in situ hybridization OT - Gene copy number variations OT - Resistance mutations OT - Targeted therapies EDAT- 2019/03/23 06:00 MHDA- 2020/04/04 06:00 CRDT- 2019/03/23 06:00 PHST- 2018/11/09 00:00 [received] PHST- 2019/02/13 00:00 [revised] PHST- 2019/02/17 00:00 [accepted] PHST- 2019/03/23 06:00 [pubmed] PHST- 2020/04/04 06:00 [medline] PHST- 2019/03/23 06:00 [entrez] AID - S1525-7304(19)30058-0 [pii] AID - 10.1016/j.cllc.2019.02.008 [doi] PST - ppublish SO - Clin Lung Cancer. 2019 Jul;20(4):e421-e429. doi: 10.1016/j.cllc.2019.02.008. Epub 2019 Feb 26.