PMID- 34271921
OWN - NLM
STAT- MEDLINE
DCOM- 20210805
LR  - 20210805
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 19
IP  - 1
DP  - 2021 Jul 16
TI  - Molecular characteristics and clinical outcomes of complex ALK rearrangements 
      identified by next-generation sequencing in non-small cell lung cancers.
PG  - 308
LID - 10.1186/s12967-021-02982-4 [doi]
LID - 308
AB  - BACKGROUND: Complex kinase rearrangement, a mutational process involving one or 
      two chromosomes with clustered rearrangement breakpoints, interferes with the 
      accurate detection of kinase fusions by DNA-based next-generation sequencing 
      (NGS). We investigated the characteristics of complex ALK rearrangements in 
      non-small cell lung cancers using multiple molecular tests. METHODS: Samples of 
      non-small cell lung cancer patients were analyzed by targeted-capture DNA-based 
      NGS with probes tilling the selected intronic regions of fusion partner genes, 
      RNA-based NGS, RT-PCR, immunohistochemistry (IHC) and fluorescence in situ 
      hybridization (FISH). RESULTS: In a large cohort of 6576 non-small cell lung 
      cancer patients, 343 (5.2%) cases harboring ALK rearrangements were identified. 
      Fourteen cases with complex ALK rearrangements were identified by DNA-based NGS 
      and classified into three types by integrating various genomic features, 
      including intergenic (n = 3), intragenic (n = 5) and "bridge joint" 
      rearrangements (n = 6). All thirteen cases with sufficient samples actually 
      expressed canonical EML4-ALK fusion transcripts confirmed by RNA-based NGS. 
      Besides, positive ALK IHC was detected in 13 of 13 cases, and 9 of 11 cases were 
      positive in FISH testing. Patients with complex ALK rearrangements who received 
      ALK inhibitors treatment (n = 6), showed no difference in progression-free 
      survival (PFS) compared with patients with canonical ALK fusions n = 36, 
      P = 0.9291). CONCLUSIONS: This study firstly reveals the molecular 
      characteristics and clinical outcomes of complex ALK rearrangements in NSCLC, 
      sensitive to ALK inhibitors treatment, and highlights the importance of utilizing 
      probes tilling the selected intronic regions of fusion partner genes in DNA-based 
      NGS for accurate fusion detection. RNA and protein level assay may be critical in 
      validating the function of complex ALK rearrangements in clinical practice for 
      optimal treatment decision.
CI  - (c) 2021. The Author(s).
FAU - Xia, Peiyi
AU  - Xia P
AD  - Department of Pathology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou University, Jian She Dong Road 1, Zhengzhou, 450052, Henan, China.
FAU - Zhang, Lan
AU  - Zhang L
AD  - Department of Pathology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou University, Jian She Dong Road 1, Zhengzhou, 450052, Henan, China.
FAU - Li, Pan
AU  - Li P
AD  - Department of Pathology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou University, Jian She Dong Road 1, Zhengzhou, 450052, Henan, China.
FAU - Liu, Enjie
AU  - Liu E
AD  - Department of Pathology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou University, Jian She Dong Road 1, Zhengzhou, 450052, Henan, China.
FAU - Li, Wencai
AU  - Li W
AD  - Department of Pathology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou University, Jian She Dong Road 1, Zhengzhou, 450052, Henan, China.
FAU - Zhang, Jianying
AU  - Zhang J
AD  - Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, 
      Zhengzhou, 450052, China.
FAU - Li, Hui
AU  - Li H
AD  - Clinical Research Division, Berry Oncology Corporation, Fuzhou, 350200, China.
FAU - Su, Xiaoxing
AU  - Su X
AD  - Clinical Research Division, Berry Oncology Corporation, Fuzhou, 350200, China.
FAU - Jiang, Guozhong
AU  - Jiang G
AUID- ORCID: 0000-0001-6306-726X
AD  - Department of Pathology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou University, Jian She Dong Road 1, Zhengzhou, 450052, Henan, China. 
      guozhongjiang@zzu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210716
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Oncogene Proteins, Fusion)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
MH  - Anaplastic Lymphoma Kinase/genetics
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics
MH  - Gene Rearrangement/genetics
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/drug therapy/genetics
MH  - Oncogene Proteins, Fusion/genetics
PMC - PMC8283930
OTO - NOTNLM
OT  - ALK fusion
OT  - Complex rearrangements
OT  - Next-generation sequencing
OT  - Non-small cell lung cancer
OT  - Targeted therapy
COIS- Hui Li and Xiaoxing Su are the employees of Berry Oncology Corporation. All other 
      authors declare no conflict of interests.
EDAT- 2021/07/18 06:00
MHDA- 2021/08/06 06:00
PMCR- 2021/07/16
CRDT- 2021/07/17 05:29
PHST- 2021/02/24 00:00 [received]
PHST- 2021/07/11 00:00 [accepted]
PHST- 2021/07/17 05:29 [entrez]
PHST- 2021/07/18 06:00 [pubmed]
PHST- 2021/08/06 06:00 [medline]
PHST- 2021/07/16 00:00 [pmc-release]
AID - 10.1186/s12967-021-02982-4 [pii]
AID - 2982 [pii]
AID - 10.1186/s12967-021-02982-4 [doi]
PST - epublish
SO  - J Transl Med. 2021 Jul 16;19(1):308. doi: 10.1186/s12967-021-02982-4.