PMID- 19204574
OWN - NLM
STAT- MEDLINE
DCOM- 20090630
LR  - 20211020
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Print)
IS  - 1556-0864 (Linking)
VI  - 4
IP  - 4
DP  - 2009 Apr
TI  - MYC and EIF3H Coamplification significantly improve response and survival of 
      non-small cell lung cancer patients (NSCLC) treated with gefitinib.
PG  - 472-8
LID - 10.1097/JTO.0b013e31819a5767 [doi]
AB  - BACKGROUND: We investigated the incidence of eukaryotic translation initiation 
      factor 3 subunit H (EIF3H) and MYC amplification in non-small cell lung cancer 
      (NSCLC) patients, and whether MYC/EIF3H increased gene copy number affected 
      response to Epidermal Growth Factor Receptor tyrosine kinase inhibitors. METHODS: 
      Metastatic NSCLC patients (n = 54) treated with gefitinib were analyzed for the 
      genomic content of EIF3H and MYC genes by fluorescence in situ hybridization 
      (FISH) using a custom-designed 3-color DNA probe set. RESULT: Amplification of 
      EIF3H (ratio EIF3H/CEP8 >2), was observed in 10 cases (18.5%), and MYC was 
      coamplified in all. MYC amplification without coamplification of EIF3H was 
      observed in 2 cases (3.7%). Receiver operating characteristic analysis was 
      conducted to identify the cutoff for MYC and EIF3H copy number best 
      discriminating sensitive and resistant populations. MYC FISH positive patients 
      (MYC+, mean > or =2.8) had a significantly higher response rate (p = 0.003), 
      longer time to progression (p = 0.01) and overall survival (OS: p = 0.02) than 
      MYC- (mean <2.8). Similarly, EIF3H FISH positive patients (EIF3H+, mean > or 
      =2.75) had a significantly higher response rate (p = 0.002), longer time to 
      progression (p = 0.01) and OS (p = 0.01) than EIF3H- (mean <2.75). CONCLUSION: 
      Our results indicate that MYC and EIF3H are frequently coamplified in NSCLC and 
      that a high copy number correlates with increased epidermal growth factor 
      receptor tyrosine kinase inhibitors sensitivity.
FAU - Cappuzzo, Federico
AU  - Cappuzzo F
AD  - Department of Oncology-Hematology, Istituto Clinico Humanitas IRCCS, Rozzano, 
      Italy. federico.cappuzzo@humanitas.it
FAU - Varella-Garcia, Marileila
AU  - Varella-Garcia M
FAU - Rossi, Elisa
AU  - Rossi E
FAU - Gajapathy, Sujatha
AU  - Gajapathy S
FAU - Valente, Marialuisa
AU  - Valente M
FAU - Drabkin, Harry
AU  - Drabkin H
FAU - Gemmill, Robert
AU  - Gemmill R
LA  - eng
GR  - P30 CA046934/CA/NCI NIH HHS/United States
GR  - P50 CA058187/CA/NCI NIH HHS/United States
GR  - P50 CA058187-12/CA/NCI NIH HHS/United States
GR  - P50 CA58187/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 (Antineoplastic Agents)
RN  - 0 (Eukaryotic Initiation Factor-3)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality
MH  - Eukaryotic Initiation Factor-3/*genetics
MH  - Female
MH  - Gefitinib
MH  - *Gene Amplification
MH  - *Genes, myc
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Quinazolines/*therapeutic use
PMC - PMC2774779
MID - NIHMS104048
COIS- Disclosure: The authors declare no conflict of interest.
EDAT- 2009/02/11 09:00
MHDA- 2009/07/01 09:00
PMCR- 2009/11/09
CRDT- 2009/02/11 09:00
PHST- 2009/02/11 09:00 [entrez]
PHST- 2009/02/11 09:00 [pubmed]
PHST- 2009/07/01 09:00 [medline]
PHST- 2009/11/09 00:00 [pmc-release]
AID - S1556-0864(15)31009-1 [pii]
AID - 10.1097/JTO.0b013e31819a5767 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2009 Apr;4(4):472-8. doi: 10.1097/JTO.0b013e31819a5767.