Luting Li1,2, Haibo Li3, Bing Li4, Jing Zhang5, Hairun Gan1,2, Ruihong Liu2,6, Xinyan Hu1,2, Pengfei Pang1,2. 1. Department of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, People's Republic of China. 2. Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, People's Republic of China. 3. Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center of Guangzhou Medical University, Guangzhou, 510627, People's Republic of China. 4. Department of Ophthalmology, The Fifth Affiliated Hospital, Sun Yat-Sen University, No. 52 Mei Hua Dong Road, Zhuhai, 519000, People's Republic of China. Pflb@sina.com. 5. Department of Interventional Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, People's Republic of China. 6. United Laboratory of Fifth Affiliated Hospital and BGI, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, People's Republic of China.
Abstract
PURPOSE: To identify the spectrum of RB1 gene mutations in 114 Chinese patients with retinoblastoma. METHODS: Genomic DNA was extracted from the peripheral blood of 114 Rb patients. Polymerase chain reactions (PCRs) followed by direct Sanger sequencing were used to screen for mutations in the RB1 gene, which contains 26 exons with flanking intronic sequences, except exon 15. Clinical data, including gender, age at diagnosis, laterality of ocular lesions, and associated symptoms, were recorded and compared. RESULTS: We identified five novel mutations in the RB1 gene. Twenty-five other mutations found in this study have been previously reported. A higher rate of RB1 mutations, with 47.3% of mutations among bilaterally affected patients vs. 6.8% within unilaterally affected patients, was also observed (p < 0.0001). Bilaterally affected patients were diagnosed earlier when compared to unilaterally affected patients (11 ± 7 months versus 20 ± 14 months, p = 0.0002). Furthermore, nonsense mutations were abundant (n = 14), followed by frameshift mutations (n = 8), splicing site mutations (n = 5), while missense mutations were few (n = 3). CONCLUSIONS: We found five novel mutations in RB1 genes, which expands the mutational spectrum of the gene. Children with bilateral Rb exhibited higher mutation rates and were diagnosed earlier than those with unilateral Rb. These findings will inform clinical diagnosis and genetic therapeutic targeting in Rb patients.
PURPOSE: To identify the spectrum of RB1 gene mutations in 114 Chinese patients with retinoblastoma. METHODS: Genomic DNA was extracted from the peripheral blood of 114 Rb patients. Polymerase chain reactions (PCRs) followed by direct Sanger sequencing were used to screen for mutations in the RB1 gene, which contains 26 exons with flanking intronic sequences, except exon 15. Clinical data, including gender, age at diagnosis, laterality of ocular lesions, and associated symptoms, were recorded and compared. RESULTS: We identified five novel mutations in the RB1 gene. Twenty-five other mutations found in this study have been previously reported. A higher rate of RB1 mutations, with 47.3% of mutations among bilaterally affected patients vs. 6.8% within unilaterally affected patients, was also observed (p < 0.0001). Bilaterally affected patients were diagnosed earlier when compared to unilaterally affected patients (11 ± 7 months versus 20 ± 14 months, p = 0.0002). Furthermore, nonsense mutations were abundant (n = 14), followed by frameshift mutations (n = 8), splicing site mutations (n = 5), while missense mutations were few (n = 3). CONCLUSIONS: We found five novel mutations in RB1 genes, which expands the mutational spectrum of the gene. Children with bilateral Rb exhibited higher mutation rates and were diagnosed earlier than those with unilateral Rb. These findings will inform clinical diagnosis and genetic therapeutic targeting in Rb patients.
Authors: Helen Dimaras; Kahaki Kimani; Elizabeth A O Dimba; Peggy Gronsdahl; Abby White; Helen S L Chan; Brenda L Gallie Journal: Lancet Date: 2012-03-12 Impact factor: 79.321
Authors: Zhao Chen; Kimberly Moran; Jennifer Richards-Yutz; Erik Toorens; Daniel Gerhart; Tapan Ganguly; Carol L Shields; Arupa Ganguly Journal: Hum Mutat Date: 2013-12-20 Impact factor: 4.878
Authors: Diane E Rushlow; Berber M Mol; Jennifer Y Kennett; Stephanie Yee; Sanja Pajovic; Brigitte L Thériault; Nadia L Prigoda-Lee; Clarellen Spencer; Helen Dimaras; Timothy W Corson; Renée Pang; Christine Massey; Roseline Godbout; Zhe Jiang; Eldad Zacksenhaus; Katherine Paton; Annette C Moll; Claude Houdayer; Anthony Raizis; William Halliday; Wan L Lam; Paul C Boutros; Dietmar Lohmann; Josephine C Dorsman; Brenda L Gallie Journal: Lancet Oncol Date: 2013-03-13 Impact factor: 41.316