PMID- 23198868
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130221
LR  - 20220330
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 5
IP  - 1
DP  - 2012 Dec 3
TI  - Incidence and patterns of ALK FISH abnormalities seen in a large unselected 
      series of lung carcinomas.
PG  - 44
LID - 10.1186/1755-8166-5-44 [doi]
AB  - BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase (ALK) gene 
      rearrangements have been reported in 2-13% of patients with non-small cell lung 
      cancer (NSCLC). Patients with ALK rearrangements do not respond to EGFR-specific 
      tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule 
      inhibitors targeting ALK. RESULTS: In this study, fluorescence in situ 
      hybridization (FISH) using a break-apart probe for the ALK gene was performed on 
      formalin fixed paraffin-embedded tissue to determine the incidence of ALK 
      rearrangements and hybridization patterns in a large unselected cohort of 1387 
      patients with a referred diagnosis of non-small cell lung cancer (1011 of these 
      patients had a histologic diagnosis of adenocarcinoma). The abnormal FISH signal 
      patterns varied from a single split signal to complex patterns. Among 49 abnormal 
      samples (49/1387, 3.5%), 32 had 1 to 3 split signals. Fifteen samples had 
      deletions of the green 5' end of the ALK signal, and 1 of these 15 samples showed 
      amplification of the orange 3' end of the ALK signal. Two patients showed a 
      deletion of the 3'ALK signal. Thirty eight of these 49 samples (38/1011, 3.7%) 
      were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients 
      with ALK rearrangements detected by FISH were confirmed to have EML4-ALK fusions 
      by multiplex RT-PCR. Among the 45 ALK-rearranged samples tested, only 1 EGFR 
      mutation (T790M) was detected. Two KRAS mutations were detected among 24 
      ALK-rearranged samples tested. CONCLUSIONS: In a large unselected series, the 
      frequency of ALK gene rearrangement detected by FISH was approximately 3.5% of 
      lung carcinoma, and 3.7% of patients with lung adenocarcinoma, with variant 
      signal patterns frequently detected. Rare cases with coexisting KRAS and EGFR 
      mutations were seen.
FAU - Dai, Zunyan
AU  - Dai Z
AD  - Department of Cytogenetics, Quest Diagnostics Nichols Institute, 14225 Newbrook 
      Drive, Chantilly, VA, 20151, USA. Zunyan.X.Dai@questdiagnostics.com.
FAU - Kelly, Joann C
AU  - Kelly JC
FAU - Meloni-Ehrig, Aurelia
AU  - Meloni-Ehrig A
FAU - Slovak, Marilyn L
AU  - Slovak ML
FAU - Boles, Debra
AU  - Boles D
FAU - Christacos, Nicole C
AU  - Christacos NC
FAU - Bryke, Christine R
AU  - Bryke CR
FAU - Schonberg, Steven A
AU  - Schonberg SA
FAU - Otani-Rosa, Jennifer
AU  - Otani-Rosa J
FAU - Pan, Qiulu
AU  - Pan Q
FAU - Ho, Albert K
AU  - Ho AK
FAU - Sanders, Heather R
AU  - Sanders HR
FAU - Zhang, Zhong J
AU  - Zhang ZJ
FAU - Jones, Dan
AU  - Jones D
FAU - Mowrey, Philip N
AU  - Mowrey PN
LA  - eng
PT  - Journal Article
DEP - 20121203
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC3576271
EDAT- 2012/12/04 06:00
MHDA- 2012/12/04 06:01
PMCR- 2012/12/03
CRDT- 2012/12/04 06:00
PHST- 2012/08/13 00:00 [received]
PHST- 2012/09/20 00:00 [accepted]
PHST- 2012/12/04 06:00 [entrez]
PHST- 2012/12/04 06:00 [pubmed]
PHST- 2012/12/04 06:01 [medline]
PHST- 2012/12/03 00:00 [pmc-release]
AID - 1755-8166-5-44 [pii]
AID - 10.1186/1755-8166-5-44 [doi]
PST - epublish
SO  - Mol Cytogenet. 2012 Dec 3;5(1):44. doi: 10.1186/1755-8166-5-44.