PMID- 16551849
OWN - NLM
STAT- MEDLINE
DCOM- 20061127
LR  - 20181201
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 12
IP  - 6
DP  - 2006 Mar 15
TI  - Somatic mutations of epidermal growth factor receptor in bile duct and 
      gallbladder carcinoma.
PG  - 1680-5
AB  - OBJECTIVE: Conventional therapies are still unsuccessful in patients with 
      carcinoma arising from the biliary tract. Somatic mutations of the epidermal 
      growth factor receptor (EGFR) gene and the activation of its downstream pathways 
      predict the sensitivity to small-molecule inhibitors in non-small cell lung 
      carcinoma. Therefore, we analyzed EGFR mutations and related pathways in 
      gallbladder and bile duct carcinomas to consider the possible application of 
      these alternative therapeutic strategies. EXPERIMENTAL DESIGN: Forty 
      paraffin-embedded samples, including intrahepatic or extrahepatic 
      cholangiocarcinoma and gallbladder carcinoma, were studied after tumor cell 
      isolation by laser microdissection and sequencing of EGFR tyrosine kinase domain 
      (exons 18-21). Activation of EGFR pathway was studied by evaluating 
      phosphorylation of mitogen-activated protein kinase and Akt. RESULTS: None of the 
      40 specimens had mutations in exon 18; one had one missense point mutation in 
      exon 19, two in exon 20, and three in exon 21. In addition, 36 of 40 specimens 
      had the same silent mutation at codon 787 in exon 20, which was also found in 
      peripheral blood cells from healthy donors. Tumor samples harboring EGFR mutation 
      had phosphorylation of one or both downstream transducers analyzed. CONCLUSIONS: 
      This is the first evidence of somatic mutations of the EGFR gene in bile duct 
      carcinoma. Our findings suggest that a subgroup of patients with 
      cholangiocarcinoma or gallbladder carcinoma exhibits somatic mutations of EGFR in 
      the tyrosine kinase domain that can elicit cell signals sustaining survival and 
      proliferation. These tumors might be further evaluated for their susceptibility 
      to small-molecule inhibitor treatment.
FAU - Leone, Francesco
AU  - Leone F
AD  - Department of Clinical Oncology, Unit of Pathology, University of Torino Medical 
      School, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy. 
      francesco.leone@ircc.it
FAU - Cavalloni, Giuliana
AU  - Cavalloni G
FAU - Pignochino, Ymera
AU  - Pignochino Y
FAU - Sarotto, Ivana
AU  - Sarotto I
FAU - Ferraris, Renato
AU  - Ferraris R
FAU - Piacibello, Wanda
AU  - Piacibello W
FAU - Venesio, Tiziana
AU  - Venesio T
FAU - Capussotti, Lorenzo
AU  - Capussotti L
FAU - Risio, Mauro
AU  - Risio M
FAU - Aglietta, Massimo
AU  - Aglietta M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Base Sequence
MH  - Bile Duct Neoplasms/genetics/metabolism/*pathology
MH  - DNA Mutational Analysis
MH  - ErbB Receptors/*genetics
MH  - Exons/genetics
MH  - Female
MH  - Gallbladder Neoplasms/genetics/metabolism/*pathology
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation/*genetics
MH  - Mutation, Missense/genetics
MH  - Phosphorylation
EDAT- 2006/03/23 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/03/23 09:00
PHST- 2006/03/23 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/03/23 09:00 [entrez]
AID - 12/6/1680 [pii]
AID - 10.1158/1078-0432.CCR-05-1692 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2006 Mar 15;12(6):1680-5. doi: 10.1158/1078-0432.CCR-05-1692.