PURPOSE: Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China and characterized by a strong association with EBV. We aimed to detect EBV DNA and cancer-related gene promoter hypermethylation in nasopharyngeal (NP) brushing samples and provide a novel noninvasive approach for NPC detection. EXPERIMENTAL DESIGN: Twenty-eight NPC cases and 26 noncancerous subjects were prospectively recruited. NP brushing samples were subjected to quantitative real-time PCR analysis of EBV DNA and methylation-specific PCR analysis of the DAP-kinase, RASSF1A, and p16 genes. RESULTS: EBV DNA quantity in NP brushing samples from NPC patients (median, 8.94 copies/actin) was significantly higher than that of controls (median, 0 copies/actin; P < 0.0001). Twenty-seven of 28 NPC patients had detectable EBV DNA in NP brushes, whereas 25 of 26 controls had undetectable or very low levels of EBV DNA. Elevated EBV DNA level in brushing samples as a tumor marker had a sensitivity of 96.4% and a specificity of 96.2% for NPC detection. Moreover, T(1) disease had a significantly lower EBV DNA level as compared with locally more advanced disease (P = 0.037). In brushing samples of NPC patients, the frequencies of DAP-kinase, RASSF1A, and p16 promoter hypermethylation were 50.0%, 39.3%, and 46.4%, respectively. Seventy-eight percent of cases showed methylation of at least one gene. No aberrant hypermethylation was detected in control samples. CONCLUSIONS: Our study demonstrated the feasibility of detecting multiple molecular tumor markers in NP brushing samples with a high sensitivity and specificity for NPC detection. It offers a powerful yet noninvasive approach for the diagnosis of NPC in high-risk populations.
PURPOSE:Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China and characterized by a strong association with EBV. We aimed to detect EBV DNA and cancer-related gene promoter hypermethylation in nasopharyngeal (NP) brushing samples and provide a novel noninvasive approach for NPC detection. EXPERIMENTAL DESIGN: Twenty-eight NPC cases and 26 noncancerous subjects were prospectively recruited. NP brushing samples were subjected to quantitative real-time PCR analysis of EBV DNA and methylation-specific PCR analysis of the DAP-kinase, RASSF1A, and p16 genes. RESULTS: EBV DNA quantity in NP brushing samples from NPCpatients (median, 8.94 copies/actin) was significantly higher than that of controls (median, 0 copies/actin; P < 0.0001). Twenty-seven of 28 NPCpatients had detectable EBV DNA in NP brushes, whereas 25 of 26 controls had undetectable or very low levels of EBV DNA. Elevated EBV DNA level in brushing samples as a tumor marker had a sensitivity of 96.4% and a specificity of 96.2% for NPC detection. Moreover, T(1) disease had a significantly lower EBV DNA level as compared with locally more advanced disease (P = 0.037). In brushing samples of NPCpatients, the frequencies of DAP-kinase, RASSF1A, and p16 promoter hypermethylation were 50.0%, 39.3%, and 46.4%, respectively. Seventy-eight percent of cases showed methylation of at least one gene. No aberrant hypermethylation was detected in control samples. CONCLUSIONS: Our study demonstrated the feasibility of detecting multiple molecular tumor markers in NP brushing samples with a high sensitivity and specificity for NPC detection. It offers a powerful yet noninvasive approach for the diagnosis of NPC in high-risk populations.
Authors: Francesca Cerimele; Traci Battle; Rebecca Lynch; David A Frank; Emma Murad; Cynthia Cohen; Nada Macaron; John Sixbey; Kenneth Smith; Randolph S Watnick; Aristidis Eliopoulos; Bahig Shehata; Jack L Arbiser Journal: Proc Natl Acad Sci U S A Date: 2004-12-20 Impact factor: 11.205
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Authors: Servi J C Stevens; Sandra A W M Verkuijlen; Bambang Hariwiyanto; Jajah Fachiroh; Dewi K Paramita; I Bing Tan; Sophia M Haryana; Jaap M Middeldorp Journal: J Clin Microbiol Date: 2005-07 Impact factor: 5.948
Authors: Joanna H Tong; David C Ng; Shuk L Chau; Ken K So; Patrick P Leung; Tin L Lee; Raymond W Lung; Michael W Chan; Anthony W Chan; Kwok W Lo; Ka F To Journal: BMC Cancer Date: 2010-06-03 Impact factor: 4.430
Authors: Maarten A Wildeman; Renske Fles; Camelia Herdini; Rai S Indrasari; Andrew D Vincent; Maesadji Tjokronagoro; Sharon Stoker; Johan Kurnianda; Baris Karakullukcu; Kartika W Taroeno-Hariadi; Olga Hamming-Vrieze; Jaap M Middeldorp; Bambang Hariwiyanto; Sofia M Haryana; I Bing Tan Journal: PLoS One Date: 2013-05-10 Impact factor: 3.240