PMID- 26636767 OWN - NLM STAT- MEDLINE DCOM- 20160626 LR - 20221207 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 12 DP - 2015 TI - Relationships between Chromosome 7 Gain, MET Gene Copy Number Increase and MET Protein Overexpression in Chinese Papillary Renal Cell Carcinoma Patients. PG - e0143468 LID - 10.1371/journal.pone.0143468 [doi] LID - e0143468 AB - 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. FAU - Yin, Xiaolu AU - Yin X AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. FAU - Zhang, Tianwei AU - Zhang T AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. FAU - Su, Xinying AU - Su X AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. FAU - Ji, Yan AU - Ji Y AD - Research & Development Information, AstraZeneca R&D, Shanghai, China. FAU - Ye, Peng AU - Ye P AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. FAU - Fu, Haihua AU - Fu H AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. FAU - Fan, Shuqiong AU - Fan S AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. FAU - Shen, Yanying AU - Shen Y AD - Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. FAU - Gavine, Paul R AU - Gavine PR AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. FAU - Gu, Yi AU - Gu Y AD - Asia & Emerging Markets iMed, AstraZeneca R&D, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151204 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Asian People/genetics MH - Carcinoma, Renal Cell/*genetics/metabolism/pathology MH - China MH - Chromosomes, Human, Pair 7/*genetics MH - Female MH - *Gene Amplification MH - Gene Expression Regulation, Neoplastic MH - Genetic Predisposition to Disease MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kidney Neoplasms/*genetics/*metabolism MH - Male MH - Prognosis MH - Proto-Oncogene Proteins c-met/*genetics MH - Up-Regulation PMC - PMC4670110 COIS- Competing Interests: Authors affiliated with AstraZeneca are full-time employees and/or stakeholders of AstraZeneca. AstraZeneca sponsored this study. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The authors declare that they have no other competing interests. EDAT- 2015/12/05 06:00 MHDA- 2016/06/28 06:00 PMCR- 2015/12/04 CRDT- 2015/12/05 06:00 PHST- 2015/06/29 00:00 [received] PHST- 2015/11/05 00:00 [accepted] PHST- 2015/12/05 06:00 [entrez] PHST- 2015/12/05 06:00 [pubmed] PHST- 2016/06/28 06:00 [medline] PHST- 2015/12/04 00:00 [pmc-release] AID - PONE-D-15-28499 [pii] AID - 10.1371/journal.pone.0143468 [doi] PST - epublish SO - PLoS One. 2015 Dec 4;10(12):e0143468. doi: 10.1371/journal.pone.0143468. eCollection 2015.