title: c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases.
abstract: The c-Met proto-oncogene encodes a receptor tyrosine kinase (TK) that promotes invasive tumor growth and metastasis. Recent studies show that the presence of c-Met gene amplification is predictive for selective c-Met TK inhibitors in gastric cancer and lung cancer. In this study, we utilized a highly quantitative PCR/ligase detection reaction technique to quantify c-Met gene copy number in primary colorectal cancer (CRC) (N=247), liver metastases (N=147), and paired normal tissues. We identified no differences in c-Met gene copy number between normal colonic mucosa and liver tissue. However, mean c-Met gene copy number was significantly elevated in CRC compared with normal mucosa (P<0.001), and in liver metastases compared with normal liver (P<0.001). Furthermore, a significant increase in c-Met was seen in liver metastases compared with primary CRC (P<0.0001). c-Met gene amplification was observed in 2% (3/177) of localized cancers, 9% (6/70) of cancers with distant metastases (P<0.02), and 18% (25/147) of liver metastases (P<0.01). Among patients treated by liver resection, there was a trend toward poorer 3-year survival in association with c-Met gene amplification (P=0.07). Slight increases in c-Met copy number can be detected in localized CRCs, but gene amplification is largely restricted to Stage IV primary cancers and liver metastases. c-Met gene amplification is linked to metastatic progression, and is a viable target for a significant subset of advanced CRC.
authors.affiliation: Department of Surgery, Colorectal Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Zhao-Shi
authors.initials: ZS
authors.lastname: Zeng
authors.forename: Martin R
authors.initials: MR
authors.lastname: Weiser
authors.forename: Eleanor
authors.initials: E
authors.lastname: Kuntz
authors.forename: Chin-Tung
authors.initials: CT
authors.lastname: Chen
authors.forename: Sajid A
authors.initials: SA
authors.lastname: Khan
authors.forename: Ann
authors.initials: A
authors.lastname: Forslund
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Nash
authors.forename: Mark
authors.initials: M
authors.lastname: Gimbel
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Alfred T
authors.initials: AT
authors.lastname: Culliford
authors.forename: Matthew
authors.initials: M
authors.lastname: D'Alessio
authors.forename: Francis
authors.initials: F
authors.lastname: Barany
authors.forename: Philip B
authors.initials: PB
authors.lastname: Paty
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met