PMID- 22282074
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20211021
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 18
DP  - 2012 Sep 15
TI  - Correlations between the percentage of tumor cells showing an anaplastic lymphoma 
      kinase (ALK) gene rearrangement, ALK signal copy number, and response to 
      crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall 
      cell lung cancer.
PG  - 4486-94
LID - 10.1002/cncr.27411 [doi]
AB  - BACKGROUND: Fluorescence in situ hybridization (FISH), using break-apart red (3') 
      and green (5') ALK (anaplastic lymphoma kinase) probes, consistently shows 
      rearrangements in <100% of tumor cells in ALK-positive (ALK+) nonsmall cell lung 
      cancer (NSCLC). Increased copy numbers of fused and rearranged signals also 
      occur. Here, correlations are explored between the percentage of ALK+ cells and 
      signal copy number and their association with response to ALK inhibition. 
      METHODS: Ninety ALK+ NSCLC cases were evaluated. The percentage of positive 
      cells, pattern of positivity (split, single red, or both), and copy number of 
      fused, isolated red and green signals were recorded. Thirty patients had received 
      crizotinib. RESULTS: Increased isolated red signal copy number (contributing to 
      both single red and split patterns of positivity) correlated with a higher 
      percentage of ALK+ cells (r = 0.743, P < .0001). Mean fused copy number was 
      negatively associated with isolated red signal copy number (r = -0.409, P < 
      .0001). Neither percentage of positive cells (r = 0.192, P = .3), nor copy number 
      of isolated red signal (r = 0.274, P = .195) correlated with maximal tumor 
      shrinkage with crizotinib. CONCLUSIONS: The strong association between increased 
      copy number of key ALK signals and percentage of positive cells suggests that the 
      <100% rate of cellular positivity in ALK+ tumors is due to technical factors, not 
      biological factors. In ALK+ tumors, neither the percentage of positive cells nor 
      signal copy number appear to be informative variables for predicting benefit from 
      ALK inhibition. The inverse relationship between fused and isolated red copy 
      number suggests ALK+ may be a distinct "near-diploid" subtype of NSCLC that 
      develops before significant chromosomal aneusomy occurs.
CI  - Copyright (c) 2012 American Cancer Society.
FAU - Camidge, D Ross
AU  - Camidge DR
AD  - University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, 
      USA. ross.camidge@ucdenver.edu
FAU - Theodoro, Mariana
AU  - Theodoro M
FAU - Maxson, Delee A
AU  - Maxson DA
FAU - Skokan, Margaret
AU  - Skokan M
FAU - O'Brien, Tara
AU  - O'Brien T
FAU - Lu, Xian
AU  - Lu X
FAU - Doebele, Robert C
AU  - Doebele RC
FAU - Baron, Anna E
AU  - Baron AE
FAU - Varella-Garcia, Marileila
AU  - Varella-Garcia M
LA  - eng
GR  - P30 CA046934/CA/NCI NIH HHS/United States
GR  - P50 CA058187/CA/NCI NIH HHS/United States
GR  - P50 CA058187-18/CA/NCI NIH HHS/United States
GR  - P50CA58187/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120126
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 53AH36668S (Crizotinib)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/enzymology/*genetics
MH  - Crizotinib
MH  - DNA Copy Number Variations
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/drug therapy/enzymology/*genetics
MH  - Male
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Pyrazoles/*therapeutic use
MH  - Pyridines/*therapeutic use
MH  - Receptor Protein-Tyrosine Kinases/*genetics
PMC - PMC3342464
MID - NIHMS344888
EDAT- 2012/01/28 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/09/15
CRDT- 2012/01/28 06:00
PHST- 2011/08/03 00:00 [received]
PHST- 2011/09/14 00:00 [revised]
PHST- 2011/09/19 00:00 [accepted]
PHST- 2012/01/28 06:00 [entrez]
PHST- 2012/01/28 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/09/15 00:00 [pmc-release]
AID - 10.1002/cncr.27411 [doi]
PST - ppublish
SO  - Cancer. 2012 Sep 15;118(18):4486-94. doi: 10.1002/cncr.27411. Epub 2012 Jan 26.