Novel mutations in the RB1 gene from Chinese families with a history of retinoblastoma

详细信息    查看全文

• 作者：Leilei Zhang ; Renbing Jia ; Junyang Zhao ; Jiayan Fan ; YiXiong Zhou…
• 关键词：Retinoblastoma ; RB1 ; Mutation ; Genetic counseling
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：36
• 期：4
• 页码：2409-2420
• 全文大小：3,044 KB
• 参考文献：1.Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, et al. Mortality from second tumors among long-term survivors of retinoblastoma. J Natl Cancer Inst. 1993;85(14):1121-.View Article PubMed
  2.Zucker JM, Desjardins L, Doz F. Retinoblastoma. Eur J Cancer. 1998;34(7):1045-. discussion 8-. doi:S0959-8049(98)00181-6.View Article PubMed
  3.Zhao J, Li S, Shi J, Wang N. Clinical presentation and group classification of newly diagnosed intraocular retinoblastoma in China. Br J Ophthalmol. 2011;95(10):1372-. doi:10.-136/?bjo.-010.-91130 .View Article PubMed
  4.Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS, et al. Retinoblastoma. Lancet. 2012;379(9824):1436-6. doi:10.-016/?S0140-6736(11)61137-9 .View Article PubMed
  5.Dryja TP, Rapaport JM, Joyce JM, Petersen RA. Molecular detection of deletions involving band q14 of chromosome 13 in retinoblastomas. Proc Natl Acad Sci U S A. 1986;83(19):7391-.View Article PubMed Central PubMed
  6.Zhao J, Dimaras H, Massey C, Xu X, Huang D, Li B, et al. Pre-enucleation chemotherapy for eyes severely affected by retinoblastoma masks risk of tumor extension and increases death from metastasis. J Clin Oncol. 2011;29(7):845-1. doi:10.-200/?JCO.-010.-2.-332 .View Article PubMed
  7.Toguchida J, McGee TL, Paterson JC, Eagle JR, Tucker S, Yandell DW, et al. Complete genomic sequence of the human retinoblastoma susceptibility gene. Genomics. 1993;17(3):535-3. doi:S0888-7543(83)71368-6.View Article PubMed
  8.Valverde JR. RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database. 2005
  9.Balmer A, Zografos L, Munier F. Diagnosis and current management of retinoblastoma. Oncogene. 2006;25(38):5341-. doi:1209622.View Article PubMed
  10.Fan JY, Han B, Qiao J, Liu BL, Ji YR, Ge SF, et al. Functional study on a novel missense mutation of the transcription factor FOXL2 causes blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). Mutagenesis. 2011;26(2):283-. doi:10.-093/?mutage/?geq086 .View Article PubMed
  11.Houdayer C, Dehainault C, Mattler C, Michaux D, Caux-Moncoutier V, Pages-Berhouet S, et al. Evaluation of in silico splice tools for decision-making in molecular diagnosis. Hum Mutat. 2008;29(7):975-2. doi:10.-002/?humu.-0765 .View Article PubMed
  12.Bertolini S, Cassanelli S, Garuti R, Ghisellini M, Simone ML, Rolleri M, et al. Analysis of LDL receptor gene mutations in Italian patients with homozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1999;19(2):408-8.View Article PubMed
  13.Cowell JK, Smith T, Bia B. Frequent constitutional C to T mutations in CGA-arginine codons in the RB1 gene produce premature stop codons in patients with bilateral (hereditary) retinoblastoma. Eur J Hum Genet. 1994;2(4):281-0.PubMed
  14.Van Orsouw NJ, Li D, van der Vlies P, Scheffer H, Eng C, Buys CH, et al. Mutational scanning of large genes by extensive PCR multiplexing and two-dimensional electrophoresis: application to the RB1 gene. Hum Mol Genet. 1996;5(6):755-1. doi:5w0369.View Article PubMed
  15.Blanquet V, Turleau C, Gross-Morand MS, Senamaud-Beaufort C, Doz F, Besmond C. Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. Hum Mol Genet. 1995;4(3):383-.View Article PubMed
  16.Xiao B, Spencer J, Clements A, Ali-Khan N, Mittnacht S, Broceno C, et al. Crystal structure of the retinoblastoma tumor suppressor protein bound to E2F and the molecular basis of its regulation. Proc Natl Acad Sci U S A. 2003;100(5):2363-. doi:10.-073/?pnas.-436813100 .View Article PubMed Central PubMed
  17.Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev. 1998;12(15):2245-2.View Article PubMed
  18.Qin XQ, Chittenden T, Livingston DM, Kaelin Jr WG. Identification of a growth suppression domain within the retinoblastoma gene product. Genes Dev. 1992;6(6):953-4.View Article PubMed
  19.Templeton DJ, Park SH, Lanier L, Weinberg RA. Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering. Proc Natl Acad Sci U S A. 1991;88(8):3033-.View Article PubMed Central PubMed
  20.Yu Y, Alwine JC. Interaction between simian virus 40 large T antigen and insulin receptor substrate 1 is disrupted by the K1 mutation, resulting in the loss of large T antigen-mediated phosphorylation of Akt. J Virol. 2008;82(9):4521-. doi:JVI.02365-07.View Article PubMed Central PubMed
  21.Talluri S, Isaac CE, Ahmad M, Henley SA, Francis SM, Martens AL, et al. A G1 checkpoint mediated by the retinoblastoma protein that is dispensable in terminal differentiation but essential for senescence. Mol Cell Biol. 2010;30(4):948-0. doi:10.-128/?MCB.-01168-09 .View Article PubMed Central PubMed
  22.Burkhart DL, Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cance
• 作者单位：Leilei Zhang (1)
  Renbing Jia (1)
  Junyang Zhao (2)
  Jiayan Fan (1)
  YiXiong Zhou (1)
  Bing Han (3)
  Xin Song (1)
  Li Wu (4)
  He Zhang (1)
  Huaidong Song (3)
  Shengfang Ge (1)
  Xianqun Fan (1)
  
  1. Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhi Zao Ju Road, Shanghai, 200011, People’s Republic of China
  2. Beijing Tongren Eye Centre, Beijing Ophthalmology & Visual Sciences Key Lab, Tongren Hospital, Capital Medical University, Beijing Economic-Technological Development Area, Beijing, 100176, People’s Republic of China
  3. Department of Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhi Zao Ju Road, Shanghai, 200011, People’s Republic of China
  4. Department of Ophthalmology, People’s Hospital, Wu Han University, No. 238 Jie Fang Road, Wu Han, 430060, People’s Republic of China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Retinoblastoma is an aggressive eye cancer that develops during infancy and is divided into two clinical types, sporadic and heritable. RB1 has been identified as the only pathological gene responsible for heritable retinoblastoma. Here, we identified 11 RB1 germline mutations in the Han pedigrees of 17 bilateral retinoblastoma patients from China. Four mutations were nonsense mutations, five were splice site mutations, and two resulted in a frame shift due to an insertion or a deletion. Three of the mutations had not been previously reported, and the p.Q344L mutation occurred in two generations of retinoblastoma patients. We investigated phenotypic–genotypic relationships for the novel mutations and showed that these mutations affected the expression, location, and function of the retinoblastoma protein. Abnormal protein localization was observed after transfection of the mutant genes. In addition, changes in the cell cycle distribution and apoptosis rates were observed when the Saos-2 cell line was transfected with plasmids encoding the mutant RB1 genes. Our findings expand the spectrum of known RB1 mutations and will benefit the investigation of RB1 mutation hotspots. Genetic counseling can be offered to families with heritable RB1 mutations.