Screening for susceptibility genes in hereditary non‑polyposis colorectal cancer

Yu,Li; Yin,Bo; Qu,Kaiying; Li,Jingjing; Jin,Qiao; Liu,Ling; Liu,Chunlan; Zhu,Yuxing; Wang,Qi; Peng,Xiaowei; Zhou,Jianda; Cao,Peiguo; Cao,Ke

doi:10.3892/ol.2018.8504

Screening for susceptibility genes in hereditary non‑polyposis colorectal cancer

Authors:
- Li Yu
- Bo Yin
- Kaiying Qu
- Jingjing Li
- Qiao Jin
- Ling Liu
- Chunlan Liu
- Yuxing Zhu
- Qi Wang
- Xiaowei Peng
- Jianda Zhou
- Peiguo Cao
- Ke Cao
View Affiliations

Affiliations: Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Plastic and Reconstructive Surgery, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Out‑patient Office, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Gynecology and Obstetrics, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Head and Neck Surgery and Oncology Plastic Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: April 16, 2018 https://doi.org/10.3892/ol.2018.8504
Pages: 9413-9419

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In the present study, hereditary non‑polyposis colorectal cancer (HNPCC) susceptibility genes were screened for using whole exome sequencing in 3 HNPCC patients from 1 family and using single nucleotide polymorphism (SNP) genotyping assays in 96 other colorectal cancer and control samples. Peripheral blood was obtained from 3 HNPCC patients from 1 family; the proband and the proband's brother and cousin. High‑throughput sequencing was performed using whole exome capture technology. Sequences were aligned against the HAPMAP, dbSNP130 and 1,000 Genome Project databases. Reported common variations and synonymous mutations were filtered out. Non‑synonymous single nucleotide variants in the 3 HNPCC patients were integrated and the candidate genes were identified. Finally, SNP genotyping was performed for the genes in 96 peripheral blood samples. In total, 60.4 Gb of data was retrieved from the 3 HNPCC patients using whole exome capture technology. Subsequently, according to certain screening criteria, 15 candidate genes were identified. Among the 96 samples that had been SNP genotyped, 92 were successfully genotyped for 15 gene loci, while genotyping for HTRA1 failed in 4 sporadic colorectal cancer patient samples. In 12 control subjects and 81 sporadic colorectal cancer patients, genotypes at 13 loci were wild‑type, namely DDX20, ZFYVE26, PIK3R3, SLC26A8, ZEB2, TP53INP1, SLC11A1, LRBA, CEBPZ, ETAA1, SEMA3G, IFRD2 and FAT1. The CEP290 genotype was mutant in 1 sporadic colorectal cancer patient and was wild‑type in all other subjects. A total of 5 of the 12 control subjects and 30 of the 81 sporadic colorectal cancer patients had a mutant HTRA1 genotype. In all 3 HNPCC patients, the same mutant genotypes were identified at all 15 gene loci. Overall, 13 potential susceptibility genes for HNPCC were identified, namely DDX20, ZFYVE26, PIK3R3, SLC26A8, ZEB2, TP53INP1, SLC11A1, LRBA, CEBPZ, ETAA1, SEMA3G, IFRD2 and FAT1.

View Figures

View References

1	Kastrinos F and Stoffel EM: History, genetics, and strategies for cancer prevention in Lynch syndrome. Clin Gastroenterol Hepatol. 12:715–727; quiz e41-43. 2014. View Article : Google Scholar : PubMed/NCBI
2	Watson P and Riley B: The tumor spectrum in the Lynch syndrome. Fam Cancer. 4:245–248. 2005. View Article : Google Scholar : PubMed/NCBI
3	Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, Kane M and Kolodner R: The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 75:1027–1038. 1993. View Article : Google Scholar : PubMed/NCBI
4	Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, Kane M, Earabino C, Lipford J, Lindblom A, et al: Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 368:258–261. 1994. View Article : Google Scholar : PubMed/NCBI
5	Whitehouse A, Meredith DM and Markham AF: DNA mismatch repair genes and their association with colorectal cancer (Review). Int J Mol Med. 1:469–474. 1998.PubMed/NCBI
6	Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, et al: Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 352:1851–1860. 2005. View Article : Google Scholar : PubMed/NCBI
7	Lynch HT and de la Chapelle A: Hereditary colorectal cancer. N Engl J Med. 348:919–932. 2003. View Article : Google Scholar : PubMed/NCBI
8	Bashyam MD, Kotapalli V, Raman R, Chaudhary AK, Yadav BK, Gowrishankar S, Uppin SG, Kongara R, Sastry RA, Vamsy M, et al: Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India. Mol Carcinog. 54:1807–1814. 2015. View Article : Google Scholar : PubMed/NCBI
9	Vasen HF, Mecklin JP, Khan PM and Lynch HT: The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 34:424–425. 1991. View Article : Google Scholar : PubMed/NCBI
10	Peltomäki P and Vasen H: Mutations associated with HNPCC predisposition-Update of ICG-HNPCC/INSiGHT mutation database. Dis Markers. 20:269–276. 2004. View Article : Google Scholar : PubMed/NCBI
11	Lindor NM: Familial colorectal cancer type X: The other half of hereditary nonpolyposis colon cancer syndrome. Surg Oncol Clin N Am. 18:637–645. 2009. View Article : Google Scholar : PubMed/NCBI
12	Nieminen TT, O'Donohue MF, Wu Y, Lohi H, Scherer SW, Paterson AD, Ellonen P, Abdel-Rahman WM, Valo S, Mecklin JP, et al: Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency. Gastroenterology. 147:595–598.e5. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yang H, Dinney CP, Ye Y, Zhu Y, Grossman HB and Wu X: Evaluation of genetic variants in microRNA-related genes and risk of bladder cancer. Cancer Res. 68:2530–2537. 2008. View Article : Google Scholar : PubMed/NCBI
14	Shin EM, Hay HS, Lee MH, Goh JN, Tan TZ, Sen YP, Lim SW, Yousef EM, Ong HT, Thike AA, et al: DEAD-box helicase DP103 defines metastatic potential of human breast cancers. J Clin Invest. 124:3807–3824. 2014. View Article : Google Scholar : PubMed/NCBI
15	Sagona AP, Nezis IP, Bache KG, Haglund K, Bakken AC, Skotheim RI and Stenmark H: A tumor-associated mutation of FYVE-CENT prevents its interaction with Beclin 1 and interferes with cytokinesis. PLoS One. 6:e170862011. View Article : Google Scholar : PubMed/NCBI
16	Wen JF BB, Zhang XB and Jiang-Ping XU: Expression and significance of ZFYVE26 in hepatocellular carcinoma. J Prac Med. 28:1939–1942. 2012.
17	Cao G, Dong W, Meng X, Liu H, Liao H and Liu S: MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by targeting PIK3R3. Tumour Biol. 36:4453–4459. 2015. View Article : Google Scholar : PubMed/NCBI
18	Wang G, Yang X, Li C, Cao X, Luo X and Hu J: PIK3R3 induces epithelial-to-mesenchymal transition and promotes metastasis in colorectal cancer. Mol Cancer Ther. 13:1837–1847. 2014. View Article : Google Scholar : PubMed/NCBI
19	Wong TS, Gao W and Chan JY: Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors. Biomed Res Int. 2014:9215642014. View Article : Google Scholar : PubMed/NCBI
20	Shahbazi J, Lock R and Liu T: Tumor protein 53-induced nuclear protein 1 enhances p53 function and represses tumorigenesis. Front Genet. 4:802013. View Article : Google Scholar : PubMed/NCBI
21	Zhou X, Ma L, Li J, Gu J, Shi Q and Yu R: Effects of SEMA3G on migration and invasion of glioma cells. Oncol Rep. 28:269–275. 2012.PubMed/NCBI
22	Valletta D, Czech B, Spruss T, Ikenberg K, Wild P, Hartmann A, Weiss TS, Oefner PJ, Müller M, Bosserhoff AK and Hellerbrand C: Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma. Carcinogenesis. 35:1407–1415. 2014. View Article : Google Scholar : PubMed/NCBI
23	Morris LG, Kaufman AM, Gong Y, Ramaswami D, Walsh LA, Turcan Ş, Eng S, Kannan K, Zou Y, Peng L, et al: Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat Genet. 45:253–261. 2013. View Article : Google Scholar : PubMed/NCBI
24	Wang JW, Gamsby JJ, Highfill SL, Mora LB, Bloom GC, Yeatman TJ, Pan TC, Ramne AL, Chodosh LA, Cress WD, et al: Deregulated expression of LRBA facilitates cancer cell growth. Oncogene. 23:4089–4097. 2004. View Article : Google Scholar : PubMed/NCBI
25	Herold T, Metzeler KH, Vosberg S, Hartmann L, Röllig C, Stölzel F, Schneider S, Hubmann M, Zellmeier E, Ksienzyk B, et al: Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis. Blood. 124:1304–1311. 2014. View Article : Google Scholar : PubMed/NCBI
26	Wu DI, Liu L, Ren C, Kong D, Zhang P, Jin X, Wang T and Zhang G: Epithelial-mesenchymal interconversions and the regulatory function of the ZEB family during the development and progression of ovarian cancer. Oncol Lett. 11:1463–1468. 2016. View Article : Google Scholar : PubMed/NCBI
27	Childs EJ, Mocci E, Campa D, Bracci PM, Gallinger S, Goggins M, Li D, Neale RE, Olson SH, Scelo G, et al: Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat Genet. 47:911–916. 2015. View Article : Google Scholar : PubMed/NCBI
28	Archer NS, Nassif NT and O'Brien BA: Genetic variants of SLC11A1 are associated with both autoimmune and infectious diseases: Systematic review and meta-analysis. Genes Immun. 16:275–283. 2015. View Article : Google Scholar : PubMed/NCBI
29	Lohi H, Kujala M, Makela S, Lehtonen E, Kestila M, Saarialho-Kere U, Markovich D and Kere J: Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8 and -A9. J Biol Chem. 277:14246–14254. 2002. View Article : Google Scholar : PubMed/NCBI
30	Zhu F, Jin L, Luo TP, Luo GH, Tan Y and Qin XH: Serine protease HtrA1 expression in human hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 9:508–512. 2010.PubMed/NCBI
31	Lehner A, Magdolen V, Schuster T, Kotzsch M, Kiechle M, Meindl A, Sweep FC, Span PN and Gross E: Downregulation of serine protease HTRA1 is associated with poor survival in breast cancer. PLoS One. 8:e603592013. View Article : Google Scholar : PubMed/NCBI