PMID- 35624360
OWN - NLM
STAT- MEDLINE
DCOM- 20220922
LR  - 20221013
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 481
IP  - 3
DP  - 2022 Sep
TI  - Detecting anaplastic lymphoma kinase (ALK) gene rearrangements with 
      next-generation sequencing remains a reliable approach in patients with 
      non-small-cell lung cancer.
PG  - 405-419
LID - 10.1007/s00428-022-03339-y [doi]
AB  - Next-generation sequencing (NGS) is rapidly becoming routine in clinical oncology 
      practice to identify therapeutic biomarkers, including gene rearrangements in 
      anaplastic lymphoma kinase (ALK). Our study investigated the concordance of ALK 
      positivity evaluated by DNA-based NGS with orthogonal ALK testing methods such as 
      fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and 
      RNA-based NGS (RNA-NGS). Thirty-eight patients with lung adenocarcinoma who were 
      detected with ALK rearrangements using DNA-NGS and also had adequate tissue 
      samples submitted for FISH, IHC, and RNA-NGS, were included in this study. Of the 
      38 patients, RNA samples from 3 patients failed quality control for RNA-NGS. The 
      concordance of ALK positivity was calculated relative to DNA-NGS results. The 
      concordance rates were 97.1% (34/35) for RNA-NGS, 94.7% (36/38) for IHC, and 
      97.4% (37/38) for FISH. DNA-NGS detected single ALK rearrangements in 14 (35.0%) 
      patients and complex ALK rearrangements in 26 (65.0%). RNA-NGS detected only 
      single transcripts of the primary ALK fusions. A novel LANCL1-ALK (L7:A20) 
      detected using DNA-NGS was detected as EML4-ALK (E13:A20) transcripts using 
      RNA-NGS. Interestingly, patients with single ALK rearrangements were more likely 
      to be detected with atypical isolated red signals (p < 0.001), while patients 
      with complex ALK rearrangements were more likely to be detected with atypical 
      split red and green signals less than 2 signal diameters apart (p < 0.001). Our 
      study highlights the reliability of NGS in the accurate detection of specific ALK 
      fusion variants and concomitant mutations that are crucial for individualized 
      treatment decisions in patients with lung cancer.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Ding, Ying
AU  - Ding Y
AD  - Department of Pathology, the First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Sun, Chang
AU  - Sun C
AD  - The First School of Clinical Medicine, Nanjing Medical University, Nanjing, 
      210029, China.
FAU - Su, Wei
AU  - Su W
AD  - The First School of Clinical Medicine, Nanjing Medical University, Nanjing, 
      210029, China.
FAU - Miao, Chen
AU  - Miao C
AD  - Department of Pathology, the First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - He, Xiao
AU  - He X
AD  - Department of Pathology, the First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Wang, Jin-Song
AU  - Wang JS
AD  - Department of Pathology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, 210000, China.
FAU - Zhang, Zhi-Hong
AU  - Zhang ZH
AUID- ORCID: 0000-0002-5779-9365
AD  - Department of Pathology, the First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China. zhangzh@njmu.edu.cn.
LA  - eng
GR  - 82172991/National Natural Science Foundation of China/
GR  - 81502089/National Natural Science Foundation of China/
GR  - 81773109/National Natural Science Foundation of China/
GR  - BK20151024/Natural Science Foundation of Jiangsu Province/
GR  - BK20151582/Natural Science Foundation of Jiangsu Province/
GR  - 21KJB320015/Natural Science Research Program for Higher Education in Jiangsu 
      Province/
PT  - Journal Article
DEP - 20220528
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
MH  - *Anaplastic Lymphoma Kinase/genetics
MH  - *Carcinoma, Non-Small-Cell Lung/pathology
MH  - Gene Rearrangement
MH  - High-Throughput Nucleotide Sequencing/methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - *Lung Neoplasms/pathology
MH  - Oncogene Proteins, Fusion/genetics
MH  - RNA/therapeutic use
MH  - Reproducibility of Results
OTO - NOTNLM
OT  - ALK rearrangement
OT  - FISH
OT  - NGS
OT  - NSCLC
EDAT- 2022/05/28 06:00
MHDA- 2022/09/23 06:00
CRDT- 2022/05/27 23:27
PHST- 2022/01/05 00:00 [received]
PHST- 2022/05/12 00:00 [accepted]
PHST- 2022/04/12 00:00 [revised]
PHST- 2022/05/28 06:00 [pubmed]
PHST- 2022/09/23 06:00 [medline]
PHST- 2022/05/27 23:27 [entrez]
AID - 10.1007/s00428-022-03339-y [pii]
AID - 10.1007/s00428-022-03339-y [doi]
PST - ppublish
SO  - Virchows Arch. 2022 Sep;481(3):405-419. doi: 10.1007/s00428-022-03339-y. Epub 
      2022 May 28.