title: Relationships between Chromosome 7 Gain, MET Gene Copy Number Increase and MET Protein Overexpression in Chinese Papillary Renal Cell Carcinoma Patients.
abstract: To investigate the relationships between Chromosome 7 gain, mesenchymal-epithelial transition factor (MET) gene copy number increase and MET protein overexpression in Chinese patients with papillary renal cell carcinoma (PRCC), immunohistochemistry (IHC), immunofluorescence (IF) and fluorescence in situ hybridization (FISH) were performed on 98 formalin-fixed, paraffin-embedded (FFPE) PRCC samples. Correlations between MET gene copy number increase, Chromosome 7 gain and MET protein overexpression were analyzed statistically. A highly significant correlation was observed between the percentage of tumor cells with MET gene copy number ≥3 and CEP7 copy number ≥3 (R2 = 0.90, p<0.001) across two subtypes of PRCC. In addition, the percentage of tumor cells with MET gene copy number ≥3 was found to increase along with increases in MET IHC score. This correlation was further confirmed in those PRCC tumor cells with average MET gene copy number >5 using combined IF and FISH methodology. Overall, this study provides evidence that Chromosome 7 gain drives MET gene copy number increase in PRCC tumors, and appears to subsequently lead to an increase in MET protein overexpression in these tumor cells. This supports MET activation as a potential therapeutic target in sporadic PRCC.
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yin
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Su
authors.affiliation: Research & Development Information, AstraZeneca R&D, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Fu
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Shuqiong
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gavine
authors.affiliation: Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
mesh_terms: D044466:Asian People / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002681:China; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met