Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance

André Lopes Carvalho, Rui Henrique, Carmen Jeronimo, Chetan S. Nayak, Ashok N. Reddy, Mohammad O. Hoque, Steven Chang, Mariana Brait, Wei Wen Jiang, Michael M. Kim, Quia Claybourne, David Goldenberg, Zubair Khan, Tanbir Khan, William H. Westra, David Sidransky, Wayne Koch, Joseph A. Califano

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Abstract

Purpose: Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pretreatment salivary rinses from HNSCC patients by using real-time quantitative methylation-specific PCR (Q-MSP). Experimental Design: Pretreatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation by using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high-risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1. Results: We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1%) showed methylation of at least one of the selected genes in the saliva DNA. Pretreatment methylated saliva DNA was not significantly associated with tumor site (P = 0.209) nor clinical stage (P = 0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (P = 0.010 and P = 0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR = 12.2; 95% CI = 1.8-80.6; P = 0.010) and overall survival (HR = 2.8; 95% CI = 1.2-6.5; P = 0.016). Conclusions: We were able to confirm an elevated rate of promoter hypermethylation in HNSCC saliva of patients by using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pretreatment saliva DNA seems to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients.

Original languageEnglish (US)
Pages (from-to)4782-4789
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number14
DOIs
StatePublished - Jul 15 2011

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Squamous Cell Carcinoma
Neck
Biomarkers
Head
Saliva
Methylation
DNA
Tumor Suppressor Genes
Survival
Tissue Inhibitor of Metalloproteinase-3
Genes
Recurrence
Polymerase Chain Reaction
Carcinoma, squamous cell of head and neck
Genetic Promoter Regions
Neoplasms
Research Design
Multivariate Analysis
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Carvalho, A. L., Henrique, R., Jeronimo, C., Nayak, C. S., Reddy, A. N., Hoque, M. O., ... Califano, J. A. (2011). Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. Clinical Cancer Research, 17(14), 4782-4789. https://doi.org/10.1158/1078-0432.CCR-11-0324
Carvalho, André Lopes ; Henrique, Rui ; Jeronimo, Carmen ; Nayak, Chetan S. ; Reddy, Ashok N. ; Hoque, Mohammad O. ; Chang, Steven ; Brait, Mariana ; Jiang, Wei Wen ; Kim, Michael M. ; Claybourne, Quia ; Goldenberg, David ; Khan, Zubair ; Khan, Tanbir ; Westra, William H. ; Sidransky, David ; Koch, Wayne ; Califano, Joseph A. / Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 14. pp. 4782-4789.
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abstract = "Purpose: Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pretreatment salivary rinses from HNSCC patients by using real-time quantitative methylation-specific PCR (Q-MSP). Experimental Design: Pretreatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation by using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high-risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1. Results: We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1{\%}) showed methylation of at least one of the selected genes in the saliva DNA. Pretreatment methylated saliva DNA was not significantly associated with tumor site (P = 0.209) nor clinical stage (P = 0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (P = 0.010 and P = 0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR = 12.2; 95{\%} CI = 1.8-80.6; P = 0.010) and overall survival (HR = 2.8; 95{\%} CI = 1.2-6.5; P = 0.016). Conclusions: We were able to confirm an elevated rate of promoter hypermethylation in HNSCC saliva of patients by using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pretreatment saliva DNA seems to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients.",
author = "Carvalho, {Andr{\'e} Lopes} and Rui Henrique and Carmen Jeronimo and Nayak, {Chetan S.} and Reddy, {Ashok N.} and Hoque, {Mohammad O.} and Steven Chang and Mariana Brait and Jiang, {Wei Wen} and Kim, {Michael M.} and Quia Claybourne and David Goldenberg and Zubair Khan and Tanbir Khan and Westra, {William H.} and David Sidransky and Wayne Koch and Califano, {Joseph A.}",
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Carvalho, AL, Henrique, R, Jeronimo, C, Nayak, CS, Reddy, AN, Hoque, MO, Chang, S, Brait, M, Jiang, WW, Kim, MM, Claybourne, Q, Goldenberg, D, Khan, Z, Khan, T, Westra, WH, Sidransky, D, Koch, W & Califano, JA 2011, 'Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance', Clinical Cancer Research, vol. 17, no. 14, pp. 4782-4789. https://doi.org/10.1158/1078-0432.CCR-11-0324

Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. / Carvalho, André Lopes; Henrique, Rui; Jeronimo, Carmen; Nayak, Chetan S.; Reddy, Ashok N.; Hoque, Mohammad O.; Chang, Steven; Brait, Mariana; Jiang, Wei Wen; Kim, Michael M.; Claybourne, Quia; Goldenberg, David; Khan, Zubair; Khan, Tanbir; Westra, William H.; Sidransky, David; Koch, Wayne; Califano, Joseph A.

In: Clinical Cancer Research, Vol. 17, No. 14, 15.07.2011, p. 4782-4789.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance

AU - Carvalho, André Lopes

AU - Henrique, Rui

AU - Jeronimo, Carmen

AU - Nayak, Chetan S.

AU - Reddy, Ashok N.

AU - Hoque, Mohammad O.

AU - Chang, Steven

AU - Brait, Mariana

AU - Jiang, Wei Wen

AU - Kim, Michael M.

AU - Claybourne, Quia

AU - Goldenberg, David

AU - Khan, Zubair

AU - Khan, Tanbir

AU - Westra, William H.

AU - Sidransky, David

AU - Koch, Wayne

AU - Califano, Joseph A.

PY - 2011/7/15

Y1 - 2011/7/15

N2 - Purpose: Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pretreatment salivary rinses from HNSCC patients by using real-time quantitative methylation-specific PCR (Q-MSP). Experimental Design: Pretreatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation by using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high-risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1. Results: We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1%) showed methylation of at least one of the selected genes in the saliva DNA. Pretreatment methylated saliva DNA was not significantly associated with tumor site (P = 0.209) nor clinical stage (P = 0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (P = 0.010 and P = 0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR = 12.2; 95% CI = 1.8-80.6; P = 0.010) and overall survival (HR = 2.8; 95% CI = 1.2-6.5; P = 0.016). Conclusions: We were able to confirm an elevated rate of promoter hypermethylation in HNSCC saliva of patients by using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pretreatment saliva DNA seems to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients.

AB - Purpose: Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pretreatment salivary rinses from HNSCC patients by using real-time quantitative methylation-specific PCR (Q-MSP). Experimental Design: Pretreatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation by using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high-risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1. Results: We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1%) showed methylation of at least one of the selected genes in the saliva DNA. Pretreatment methylated saliva DNA was not significantly associated with tumor site (P = 0.209) nor clinical stage (P = 0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (P = 0.010 and P = 0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR = 12.2; 95% CI = 1.8-80.6; P = 0.010) and overall survival (HR = 2.8; 95% CI = 1.2-6.5; P = 0.016). Conclusions: We were able to confirm an elevated rate of promoter hypermethylation in HNSCC saliva of patients by using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pretreatment saliva DNA seems to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients.

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