c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases.

Titlec-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases.
Publication TypeJournal Article
Year of Publication2008
AuthorsZeng Z-S, Weiser MR, Kuntz E, Chen C-T, Khan SA, Forslund A, Nash GM, Gimbel M, Yamaguchi Y, Culliford AT, D'Alessio M, Barany F, Paty PB
JournalCancer Lett
Date Published2008 Jul 8
KeywordsCell Line, Tumor, Colorectal Neoplasms, Female, Gene Amplification, Gene Dosage, Humans, Liver Neoplasms, Male, Middle Aged, Polymerase Chain Reaction, Proto-Oncogene Proteins c-met

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.

Alternate JournalCancer Lett.
PubMed ID18395971
Grant ListZ PO1 CA 65930-05 / CA / NCI NIH HHS / United States

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