Computational analysis of CDH1 missense mutations in the cause of hereditary diffuse gastric cancer
DOI:
https://doi.org/10.3329/bjp.v8i2.14679Keywords:
Missense mutation, SIFT, Polyphen 2.0, I-Mutant, SNPs&Go, Molecular DockingAbstract
In this present study, we computationally identified the germline missense mutation in the E-cadherin (CDH1) gene causing hereditary diffuse gastric cancer (HDGC). The analysis was initiated with SIFT followed by PolyPhen and I-Mutant2.0 programs with the help of 68 CDH1 variants retrieved from dbSNP. The analysis indicates that 10 variants such as P201R, A298T, E336D, C695R, N751K, Y755C, D768N, G879S, D882N and R169H were commonly found to be less stable and damaging by SIFT, PolyPhen and I-Mutant2.0 programs. Furthermore, SNPs&GO was used to predict the disease related mutations from the protein sequence. Finally, the affinities for the cetuximab with CDH1 variants were examined by using molecular docking algorithm. The result showed that P201R, A298T, E336D and R169H variants were found to be highly significant than the other mutations considered in our analysis. We sincerely hope that these findings certainly helpful for the experimental biologist working in HDGC drug development.
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Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL Workspace: A web-based environment for protein structure homology modeling. Bioinformatics 2006; 22: 195-201.
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The protein data bank. Nucleic Acids Res. 2000; 28: 235-42.
Berx G, Becker K-F, Höfler H, van Roy F. Mutations of the human E-cadherin (CDH1) Gene. Human Mutation. 1998; 12: 224-32.
Brooks-Wilson AR, Kaurah P, Suriano G, Leach S, Senz J, Grehan N, Butterfield YSN, Jeyes J, Schinas J, Bacani J, Kelsey M, Ferreira P, MacGillivray B, MacLeod P, Micek M, Ford J, Foulkes W, Australie K, Greenberg C, LaPointe M, Gilpin C, Nikkel S, Gilchrist D, Hughes R, Jackson CE, Monaghan KG, Oliveira MJ, Seruca R, Gallinger S, Caldas C, Huntsman D. Germline E-cadherin mutations in hereditary diffuse gastric cancer: Assessment of 42 new families and review of genetic screening criteria. Journal of Medical Genetics. 2004; 41: 508-17.
Calabrese R, Capriotti E, Fariselli P, Martelli PL, Casadio R. Functional annotations improve the predictive score of human disease-related mutations in proteins. Human Mutation. 2009; 30: 1237-44.
Capriotti E, Fariselli P, Casadio R. I-Mutant2.0: Predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Res. 2005; 33: 306-10.
Corso G, Marrelli D, Pascale V, Vindigni C, Roviello F. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: Metanalysis and systematic review of the literature. BMC Cancer. 2012; 12: 8.
Graziano F, Arduini F, Ruzzo A, Bearzi I, Humar B, More H, Silva R, Muretto P, Guilford P, Testa E, Mari D, Magnani M, Cascinu S. Prognostic analysis of E-cadherin gene promoter hypermethylation in patients with surgically resected, node-positive, diffuse gastric cancer. Clin Cancer Res. 2004; 10: 2784-89.
Heindl S, Eggenstein E, Keller S, Kneissl J, Keller G, Mutze K, Rauser S, Gasteiger G, Drexler I, Hapfelmeier A, Höfler H, Luber B. Relevance of MET activation and genetic alterations of KRAS and E-cadherin for Cetuximab sensitivity of gastric cancer cell lines. J Cancer Res Clin Oncol. 2012; 138: 843-58.
Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N, Suriano G, Zaor S, Van Manen L, Gilpin C, Nikkel S, Connolly-Wilson M, Weissman S, Rubinstein WS, Sebold C, Greenstein R, Stroop J, Yim D, Panzini B, McKinnon W, Greenblatt M, Wirtzfeld D, Fontaine D, Coit D, Yoon S, Chung D, Lauwers G, Pizzuti A, Vaccaro C, Redal MA, Oliveira C, Tischkowitz M, Olschwang S, Gallinger S, Lynch H, Green J, Ford J, Pharoah P, Fernandez B, Huntsman D. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. J Am Med Assoc. 2007; 297: 2360-72.
Keller G, Vogelsang H, Becker I, Hutter J, Ott K, Candidus S, Grundei T, Becker K-F, Mueller J, Siewert JR, Höfler H. Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-Cadherin germline mutation. Am J Pathol. 1999; 155: 337-42.
Kim HC, Wheeler JMD, Kim JC, Ilyas M, Beck NE, Kim BS, Park KC, Bodmer WF. The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea. Gut 2000; 47: 262-67.
Lordick F, Luber B, Lorenzen S, Hegewisch-Becker S, Folprecht G, Wöll E Decker T, Endlicher E, Röthling N, Schuster T, Keller G, Fend F, and Peschel C. Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: A phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Brit J Cancer 2010; 102: 500-05.
Mashiach E, Schneidman-Duhovny D, Andrusier N, Nussinov R, Wolfson H FireDock: A web server for fast interaction refinement in molecular docking. Nucleic Acids Res. 2008; 36: W229-32.
More H, Humar B, Weber W, Ward R, Christian A, Lintott C, Graziano F, Ruzzo A-M, Acosta E, Boman B, Harlan M, Ferreira P, Seruca R, Suriano G, Guilford P. Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene. Human Mutation. 2007; 28: 203.
Ng PC, Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003; 31: 3812-14.
Nishiyama M, Wada S. Docetaxel: its role in current and future treatments for advanced gastric cancer. Gastric Cancer 2009; 12: 132-41.
Oliveira C, Suriano G, Ferreira P, Canedo P, Kaurah P, Mateus R, Ferreira A, António C. Ferreira, Oliveira MJ, Figueiredo C, Carneiro F, Keller G, Huntsman D, Machado JC, Seruca R. Genetic screening for familial gastric cancer. Hereditary Cancer Clin Practice 2004; 2: 51-64.
Pe?ina-laus N. Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cancer Cell Int. 2003; 3: 17.
Qian X, Karpova T, Sheppard AM, McNally J, Lowy DR. E-cadherin mediated adhesion inhibits ligand dependent activation of diverse receptor tyrosine kinases. EMBO J. 2004; 23: 1739-48.
Ramensky V, Bork P, Sunyaev S. Human non-synonymous SNPs: Server and survey. Nucleic Acids Res. 2002; 30: 3894-900.
Smigielski EM, Sirotkin K, Ward M, Sherry ST. dbSNP: A database of single nucleotide polymorphisms. Nucleic Acids Res. 2000; 28: 352-55.
Teng S, Madej T, Panchenko A, Alexov E. Modeling effects of human single nucleotide polymorphisms on protein-protein interactions. Biophy J. 2009; 96: 2178-88.
Zhang Y, Liu X, Fan Y, Ding J, Xu A, Zhou X, Hu X, Zhu M, Zhang X, Li S, Wu J, Cao H, Li J, Wang Y. Germline mutations and polymorphic variants in MMR, E-cadherin and MYH genes associated with familial gastric cancer in Jiangsu of China. Int J Cancer. 2006; 119: 2592-96.
Zhang Y, Wang Q. Sunitinib reverse multidrug resistance in gastric cancer cells by modulating Stat3 and inhibiting P-gp Function. Cell Biochem Biophy. 2013; 2013.
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