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Published in: Medical Oncology 12/2014

01-12-2014 | Original Paper

Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer patients

Authors: Xu Cao, Xuan Hong, Xiaoli Jia, Liping Zhang, Gang Chen

Published in: Medical Oncology | Issue 12/2014

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Abstract

MET has been suggested to have an intimate relationship with small cell lung cancer (SCLC) and might be a promising therapeutic target. To date, relatively limited reports have been explored on MET mutational status in SCLC patients. To investigate the relationship between MET mutations and SCLC, 68 Chinese patients surgically treated for SCLC were enrolled. MET mutational analyses were performed in tumors, adjacent normal tissues as well as in lymph nodes with no metastasis nonadherent to tumor tissues using Sanger sequencing after PCR. The same mutation types were found in tumors, adjacent normal tissues as well as lymph nodes, including the only missense mutation N375S encoding semaphorin domain in exon 2 in 4 patients (5.9 %), one single-nucleotide polymorphism (SNP) rs35775721: C>T also encoding semaphorin domain as heterozygous in 10 cases (14.7 %) and another SNP rs41736: C>T encoding tyrosine kinase domain in exon 20 existing in 49 cases (72.1 %). In survival analysis, the wild genotype CC-carriers of rs41736 conferred a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to CT + TT-carriers (HR 0.455, 95 % CI 0.229–0.904; HR 0.226, 95 % CI 0.099–0.515, for PFS and OS, respectively) in limited-stage SCLC patients. We also found that the lymph node status was significantly associated with OS, and the shorter OS was present in positive group (HR 2.187, 95 % CI 1.170–4.088). In this study, rs41736 polymorphism of MET was first found to be associated with prognosis of limited-stage SCLC patients and could be considered as a prognostic marker for limited-stage SCLC.
Literature
1.
go back to reference Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.PubMedCrossRef Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.PubMedCrossRef
2.
go back to reference Chute JP, Chen T, Feigal E, Simon R, Johnson BE. Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol. 1999;17:1794–801.PubMed Chute JP, Chen T, Feigal E, Simon R, Johnson BE. Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol. 1999;17:1794–801.PubMed
3.
go back to reference Merrill RM, Henson DE, Barnes M. Conditional survival among patients with carcinoma of the lung. Chest. 1999;116:697–703.PubMedCrossRef Merrill RM, Henson DE, Barnes M. Conditional survival among patients with carcinoma of the lung. Chest. 1999;116:697–703.PubMedCrossRef
4.
go back to reference Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, et al. Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J. 1991;10:2867–78.PubMedCentralPubMed Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, et al. Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J. 1991;10:2867–78.PubMedCentralPubMed
5.
go back to reference Rosen EM, Nigam SK, Goldberg ID. Scatter factor and the c-met receptor: a paradigm for mesenchymal/epithelial interaction. J Cell Biol. 1994;127:1783–7.PubMedCrossRef Rosen EM, Nigam SK, Goldberg ID. Scatter factor and the c-met receptor: a paradigm for mesenchymal/epithelial interaction. J Cell Biol. 1994;127:1783–7.PubMedCrossRef
6.
go back to reference Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010;11:834–48.PubMedCrossRef Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010;11:834–48.PubMedCrossRef
7.
go back to reference Jeffers M, Rong S, Vande Woude GF. Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion/metastasis. J Mol Med (Berl). 1996;74:505–13.CrossRef Jeffers M, Rong S, Vande Woude GF. Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion/metastasis. J Mol Med (Berl). 1996;74:505–13.CrossRef
8.
go back to reference Camp RL, Rimm EB, Rimm DL. Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma. Cancer. 1999;86:2259–65.PubMedCrossRef Camp RL, Rimm EB, Rimm DL. Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma. Cancer. 1999;86:2259–65.PubMedCrossRef
9.
go back to reference Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, et al. Clinical significance of hepatocyte growth factor and c-Met expression in extrahepatic biliary tract cancers. Oncol Rep. 1999;6:1051–6.PubMed Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, et al. Clinical significance of hepatocyte growth factor and c-Met expression in extrahepatic biliary tract cancers. Oncol Rep. 1999;6:1051–6.PubMed
10.
go back to reference Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85:1894–902.PubMedCrossRef Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85:1894–902.PubMedCrossRef
11.
go back to reference Siegfried JM, Weissfeld LA, Singh-Kaw P, Weyant RJ, Testa JR, Landreneau RJ. Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer. Cancer Res. 1997;57:433–9.PubMed Siegfried JM, Weissfeld LA, Singh-Kaw P, Weyant RJ, Testa JR, Landreneau RJ. Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer. Cancer Res. 1997;57:433–9.PubMed
12.
go back to reference Kubo T, Yamamoto H, Lockwood WW, Valencia I, Soh J, Peyton M, et al. MET gene amplification or EGFR mutation activate MET in lung cancers untreated with EGFR tyrosine kinase inhibitors. Int J Cancer. 2009;124:1778–84.PubMedCentralPubMedCrossRef Kubo T, Yamamoto H, Lockwood WW, Valencia I, Soh J, Peyton M, et al. MET gene amplification or EGFR mutation activate MET in lung cancers untreated with EGFR tyrosine kinase inhibitors. Int J Cancer. 2009;124:1778–84.PubMedCentralPubMedCrossRef
13.
go back to reference Go H, Jeon YK, Park HJ, Sung SW, Seo JW, Chung DH. High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer. J Thorac Oncol. 2010;5:305–13.PubMedCrossRef Go H, Jeon YK, Park HJ, Sung SW, Seo JW, Chung DH. High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer. J Thorac Oncol. 2010;5:305–13.PubMedCrossRef
14.
go back to reference Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA. 2007;104:20932–7.PubMedCentralPubMedCrossRef Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA. 2007;104:20932–7.PubMedCentralPubMedCrossRef
15.
go back to reference Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039–43.PubMedCrossRef Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039–43.PubMedCrossRef
16.
go back to reference Park WS, Dong SM, Kim SY, Na EY, Shin MS, Pi JH, et al. Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res. 1999;59:307–10.PubMed Park WS, Dong SM, Kim SY, Na EY, Shin MS, Pi JH, et al. Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res. 1999;59:307–10.PubMed
17.
go back to reference Di Renzo MF, Olivero M, Martone T, Maffe A, Maggiora P, Stefani AD, et al. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene. 2000;19:1547–55.PubMedCrossRef Di Renzo MF, Olivero M, Martone T, Maffe A, Maggiora P, Stefani AD, et al. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene. 2000;19:1547–55.PubMedCrossRef
18.
go back to reference Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, et al. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res. 2003;63:6272–81.PubMed Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, et al. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res. 2003;63:6272–81.PubMed
19.
go back to reference Sattler M, Reddy MM, Hasina R, Gangadhar T, Salgia R. The role of the c-Met pathway in lung cancer and the potential for targeted therapy. Ther Adv Med Oncol. 2011;3:171–84.PubMedCentralPubMedCrossRef Sattler M, Reddy MM, Hasina R, Gangadhar T, Salgia R. The role of the c-Met pathway in lung cancer and the potential for targeted therapy. Ther Adv Med Oncol. 2011;3:171–84.PubMedCentralPubMedCrossRef
20.
go back to reference Kong-Beltran M, Seshagiri S, Zha J, Zhu W, Bhawe K, Mendoza N, et al. Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res. 2006;66:283–9.PubMedCrossRef Kong-Beltran M, Seshagiri S, Zha J, Zhu W, Bhawe K, Mendoza N, et al. Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res. 2006;66:283–9.PubMedCrossRef
21.
go back to reference Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, Fox EA, et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res. 2005;65:1479–88.PubMedCrossRef Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, Fox EA, et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res. 2005;65:1479–88.PubMedCrossRef
22.
go back to reference Krishnaswamy S, Kanteti R, Duke-Cohan JS, Loganathan S, Liu W, Ma PC, et al. Ethnic differences and functional analysis of MET mutations in lung cancer. Clin Cancer Res. 2009;15:5714–23.PubMedCentralPubMedCrossRef Krishnaswamy S, Kanteti R, Duke-Cohan JS, Loganathan S, Liu W, Ma PC, et al. Ethnic differences and functional analysis of MET mutations in lung cancer. Clin Cancer Res. 2009;15:5714–23.PubMedCentralPubMedCrossRef
23.
go back to reference Tyner JW, Fletcher LB, Wang EQ, Yang WF, Rutenberg-Schoenberg ML, Beadling C, et al. MET receptor sequence variants R970C and T992I lack transforming capacity. Cancer Res. 2010;70:6233–7.PubMedCentralPubMedCrossRef Tyner JW, Fletcher LB, Wang EQ, Yang WF, Rutenberg-Schoenberg ML, Beadling C, et al. MET receptor sequence variants R970C and T992I lack transforming capacity. Cancer Res. 2010;70:6233–7.PubMedCentralPubMedCrossRef
24.
go back to reference Rossi A, Di Maio M, Chiodini P, Rudd RM, Okamoto H, Skarlos DV, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30:1692–8.PubMedCrossRef Rossi A, Di Maio M, Chiodini P, Rudd RM, Okamoto H, Skarlos DV, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30:1692–8.PubMedCrossRef
25.
go back to reference Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, et al. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene. 2000;19:4947–53.PubMedCrossRef Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, et al. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene. 2000;19:4947–53.PubMedCrossRef
26.
go back to reference Neklason DW, Done MW, Sargent NR, Schwartz AG, Anton-Culver H, Griffin CA, et al. Activating mutation in MET oncogene in familial colorectal cancer. BMC Cancer. 2011;11:424.PubMedCentralPubMedCrossRef Neklason DW, Done MW, Sargent NR, Schwartz AG, Anton-Culver H, Griffin CA, et al. Activating mutation in MET oncogene in familial colorectal cancer. BMC Cancer. 2011;11:424.PubMedCentralPubMedCrossRef
27.
go back to reference Lee CC, Yamada KM. Alternatively spliced juxtamembrane domain of a tyrosine kinase receptor is a multifunctional regulatory site—deletion alters cellular tyrosine phosphorylation pattern and facilitates binding of phosphatidylinositol-3-Oh kinase to the hepatocyte growth-factor receptor. J Biol Chem. 1995;270:507–10.PubMedCrossRef Lee CC, Yamada KM. Alternatively spliced juxtamembrane domain of a tyrosine kinase receptor is a multifunctional regulatory site—deletion alters cellular tyrosine phosphorylation pattern and facilitates binding of phosphatidylinositol-3-Oh kinase to the hepatocyte growth-factor receptor. J Biol Chem. 1995;270:507–10.PubMedCrossRef
28.
go back to reference Voortman J, Harada T, Chang RP, Killian JK, Suuriniemi M, Smith WI, et al. Detection and therapeutic implications of c-Met mutations in small cell lung cancer and neuroendocrine tumors. Curr Pharm Des. 2013;19:833–40.PubMedCrossRef Voortman J, Harada T, Chang RP, Killian JK, Suuriniemi M, Smith WI, et al. Detection and therapeutic implications of c-Met mutations in small cell lung cancer and neuroendocrine tumors. Curr Pharm Des. 2013;19:833–40.PubMedCrossRef
29.
go back to reference Campbell DB, Sutcliffe JS, Ebert PJ, Militerni R, Bravaccio C, Trillo S, et al. A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci USA. 2006;103:16834–9.PubMedCentralPubMedCrossRef Campbell DB, Sutcliffe JS, Ebert PJ, Militerni R, Bravaccio C, Trillo S, et al. A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci USA. 2006;103:16834–9.PubMedCentralPubMedCrossRef
30.
go back to reference Uzunoglu FG, Heumann A, Musici S, Kutup A, Koenig A, Roch N, et al. The T393C polymorphism of GNAS1 is a predictor for relapse and survival in resectable non-small cell lung cancer. Lung Cancer. 2013;79:151–5.PubMedCrossRef Uzunoglu FG, Heumann A, Musici S, Kutup A, Koenig A, Roch N, et al. The T393C polymorphism of GNAS1 is a predictor for relapse and survival in resectable non-small cell lung cancer. Lung Cancer. 2013;79:151–5.PubMedCrossRef
31.
go back to reference Capon F, Allen MH, Ameen M, Burden AD, Tillman D, Barker JN, et al. A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum Mol Genet. 2004;13:2361–8.PubMedCrossRef Capon F, Allen MH, Ameen M, Burden AD, Tillman D, Barker JN, et al. A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum Mol Genet. 2004;13:2361–8.PubMedCrossRef
32.
go back to reference Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet. 2003;12:205–16.PubMedCrossRef Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet. 2003;12:205–16.PubMedCrossRef
33.
go back to reference Tierney MJ, Medcalf RL. Plasminogen activator inhibitor type 2 contains mRNA instability elements within exon 4 of the coding region—sequence homology to coding region instability determinants in other mRNAs. J Biol Chem. 2001;276:13675–84.PubMed Tierney MJ, Medcalf RL. Plasminogen activator inhibitor type 2 contains mRNA instability elements within exon 4 of the coding region—sequence homology to coding region instability determinants in other mRNAs. J Biol Chem. 2001;276:13675–84.PubMed
34.
go back to reference Frey UH, Eisenhardt A, Lummen G, Rubben H, Jockel KH, Schmid KW, et al. The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer. Cancer Epidemiol Biomark Prev. 2005;14:871–7.CrossRef Frey UH, Eisenhardt A, Lummen G, Rubben H, Jockel KH, Schmid KW, et al. The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer. Cancer Epidemiol Biomark Prev. 2005;14:871–7.CrossRef
Metadata
Title
Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer patients
Authors
Xu Cao
Xuan Hong
Xiaoli Jia
Liping Zhang
Gang Chen
Publication date
01-12-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 12/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0333-9

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