PMID- 26536196
OWN - NLM
STAT- MEDLINE
DCOM- 20160920
LR  - 20181202
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Print)
IS  - 1556-0864 (Linking)
VI  - 10
IP  - 11
DP  - 2015 Nov
TI  - Clinical Implications of Variant ALK FISH Rearrangement Patterns.
PG  - 1648-52
LID - 10.1097/JTO.0000000000000665 [doi]
AB  - INTRODUCTION: Break-apart fluorescence in situ hybridization (FISH) is the 
      FDA-approved assay for detecting anaplastic lymphoma kinase (ALK) rearrangements 
      in non-small-cell lung cancer (NSCLC), identifying patients who can gain dramatic 
      benefit from ALK kinase inhibitors. Assay interpretation can be technically 
      challenging, and either splitting of the 5' and 3' probes or loss of the 5' probe 
      constitute rearrangement. We hypothesized that there may be clinical differences 
      depending on rearrangement pattern on FISH. METHODS: An IRB-approved database of 
      NSCLC patients at Dana-Farber Cancer Institute was queried for ALK rearrangement. 
      Clinical characteristics and response to crizotinib were reviewed. 
      Immunohistochemistry (IHC) and targeted next-generation sequencing (NGS) were 
      obtained when available. RESULTS: Of 1614 NSCLC patients with ALK testing, 82 
      patients (5.1%) had ALK rearrangement by FISH: 30 patients with split signals, 25 
      patients with 5' deletion, and 27 patients with details unavailable. Patients 
      with 5' deletion were older (p = 0.01) and tended to have more extensive smoking 
      histories (p = 0.08). IHC was positive for ALK rearrangement in all 27 patients 
      with FISH split signals, whereas three of 21 patients with FISH 5' deletion had 
      negative IHC (p = 0.05). Targeted NGS on two of three cases with discordant FISH 
      and IHC results did not identify ALK rearrangement, instead finding driver 
      mutations in EGFR and KRAS. Patients with 5' deletion treated with crizotinib had 
      a smaller magnitude of tumor response (p = 0.03). CONCLUSIONS: Patients with 5' 
      deletion on ALK FISH harbor features less typical of ALK-rearranged tumors, 
      potentially indicating that some cases with this variant are false positives. 
      Corroborative testing with IHC or NGS may be beneficial.
FAU - Gao, Xin
AU  - Gao X
AD  - *Brigham and Women's Hospital, Boston, Massachusetts; and daggerDana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Sholl, Lynette M
AU  - Sholl LM
FAU - Nishino, Mizuki
AU  - Nishino M
FAU - Heng, Jennifer C
AU  - Heng JC
FAU - Janne, Pasi A
AU  - Janne PA
FAU - Oxnard, Geoffrey R
AU  - Oxnard GR
LA  - eng
GR  - K23 CA157631/CA/NCI NIH HHS/United States
GR  - R01 CA136851/CA/NCI NIH HHS/United States
GR  - 1K23CA157631/CA/NCI NIH HHS/United States
GR  - R01CA136851/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 53AH36668S (Crizotinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/pathology
MH  - Crizotinib
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lung Neoplasms/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/administration & dosage/*therapeutic use
MH  - Pyrazoles/administration & dosage/*therapeutic use
MH  - Pyridines/administration & dosage/*therapeutic use
MH  - Young Adult
PMC - PMC4634010
MID - NIHMS710832
EDAT- 2015/11/05 06:00
MHDA- 2016/09/22 06:00
PMCR- 2016/11/01
CRDT- 2015/11/05 06:00
PHST- 2015/11/05 06:00 [entrez]
PHST- 2015/11/05 06:00 [pubmed]
PHST- 2016/09/22 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - S1556-0864(15)35079-6 [pii]
AID - 10.1097/JTO.0000000000000665 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2015 Nov;10(11):1648-52. doi: 10.1097/JTO.0000000000000665.