Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach

被引：15
作者：
Mutalib N.-S.A. [1 ]
Syafruddin S.E. [1 ]
Zain R.R.M. [2 ]
Dali A.Z.H.M. [3 ]
Yunos R.I.M. [1 ]
Saidin S. [1 ]
Jamal R. [1 ]
Mokhtar N.M. [1 ,4 ]
机构：
[1] UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur
[2] Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur
[3] Department of Obstetrics and Gynecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur
[4] Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd Aziz, Kuala Lumpur
来源：
BMC Research Notes | / 7卷 / 1期
关键词：
Ion AmpliSeq Cancer Hotspot Panel; Next generation sequencing; Personal Genome Machine (PGM™); Serous ovarian cancer;
D O I：
10.1186/1756-0500-7-805
中图分类号：
学科分类号：
摘要：
Background: High grade serous ovarian cancer is one of the poorly characterized malignancies. This study aimed to elucidate the mutational events in Malaysian patients with high grade serous ovarian cancer by performing targeted sequencing on 50 cancer hotspot genes. Results: Nine high grade serous ovarian carcinoma samples and ten normal ovarian tissues were obtained from Universiti Kebangsaan Malaysia Medical Center (UKMMC) and the Kajang Hospital. The Ion AmpliSeq Cancer Hotspot Panel v2 targeting "mutation-hotspot region" in 50 most common cancer-Associated genes was utilized. A total of 20 variants were identified in 12 genes. Eleven (55%) were silent alterations and nine (45%) were missense mutations. Six of the nine missense mutations were predicted to be deleterious while the other three have low or neutral protein impact. Eight genes were altered in both the tumor and normal groups (APC, EGFR, FGFR3, KDR, MET, PDGFRA, RET and SMO) while four genes (TP53, PIK3CA, STK11 and KIT) were exclusively altered in the tumor group. TP53 alterations were present in all the tumors but not in the normal group. Six deleterious mutations in TP53 (p.R175H, p.H193R, p.Y220C, p.Y163C, p.R282G and p.Y234H) were identified in eight serous ovarian carcinoma samples and none in the normal group. Conclusion: TP53 remains as the most frequently altered gene in high grade serous ovarian cancer and Ion Torrent Personal Genome Machine (PGM) in combination with Ion Ampliseq Cancer Hotspot Panel v2 were proven to be instrumental in identifying a wide range of genetic alterations simultaneously from a minute amount of DNA. However, larger series of validation targeting more genes are necessary in order to shed a light on the molecular events underlying pathogenesis of this cancer. © 2014 Ab Mutalib et al.
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共 30 条
[1]  
McCourt, C.M., McArt, D.G., Mills, K., Catherwood, M.A., Maxwell, P., Waugh, D.J., Hamilton, P., Salto-Tellez, M., Validation of next generation sequencing technologies in comparison to current diagnostic gold standards for BRAF EGFR and KRAS mutational analysis (2013) PLoS One, 8, p. e69604
[2]  
Sanger, F., Nicklen, S., Coulson, A.R., DNA sequencing with chain terminating inhibitors (1977) Proc Natl Acad Sci U S A, 74, pp. 5463-5467
[3]  
Meldrum, C., Doyle, M.A., Tothill, R.W., Next-generation sequencing for cancer diagnostics: A practical perspective (2011) Clin Biochem Rev, 32, pp. 177-195
[4]  
Choi, M., Scholl, U.I., Ji, W., Liu, T., Tikhonova, I.R., Zumbo, P., Nayir, A., Lifton, R.P., Genetic diagnosis by whole exome capture and massively parallel DNA sequencing (2009) Proc Natl Acad Sci U S A, 106, pp. 19096-19101
[5]  
Zainal Ariffin, O., Nor Saleha, I.T., (2007) NCR Report, , Malaysia: Ministry of Health, 2011
[6]  
Ferlay, J., Soerjomataram, I., Ervik, M., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Bray, F., (2013) GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base 11 [Internet], , http://globocan.iarc.fr, Lyon, France: International Agency for Research on Cancer, accessed on 1/February/2014
[7]  
Ayhan, A., Kurman, R.J., Yemelyanova, A., Vang, R., Logani, S., Seidman, J.D., Shih, I.M., Defining the cut point between low-grade and high-grade ovarian serous carcinomas: A clinicopathologic and molecular genetic analysis (2009) Am J Surg Pathol, 33, pp. 1220-1224
[8]  
Vang, R., Shih, I.M., Kurman, R.J., Ovarian low-grade and high-grade serous carcinoma: Pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems (2009) Adv Anat Pathol, 16, pp. 267-282
[9]  
Gershenson, D.M., Sun, C.C., Lu, K.H., Coleman, R.L., Sood, A.K., Malpica, A., Deavers, M.T., Bodurka, D.C., Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary (2006) Obstet Gynecol, 108, pp. 361-368
[10]  
Malpica, A., Deavers, M.T., Lu, K., Bodurka, D.C., Atkinson, E.N., Gershenson, D.M., Silva, E.G., Grading ovarian serous carcinoma using a two-Tier system (2004) Am J Surg Pathol, 28, pp. 496-504
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