Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma

André Lopes Carvalho, Carmen Jeronimo, Michael Kim, Rui Henrique, Zhe Zhang, Mohammad O. Hoque, Steve Chang, Mariana Brait, Chetan S. Nayak, Wei Wen Jiang, Quia Claybourne, Yutaka Tokumaru, Juna Lee, David Goldenberg, Elizabeth Garrett-Mayer, Steven Goodman, Chul So Moon, Wayne Koch, William H. Westra, David Sidransky & 1 others Joseph A. Califano

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Purpose: To evaluate aberrant promoter hypermethylation of candidate tumor suppressor genes as a means to detect epigenetic alterations specific to solid tumors, including head and neck squamous cell carcinoma (HNSCC). Experimental Design: Using promoter regions identified via a candidate gene and discovery approach, we evaluated the ability of an expanded panel of CpG-rich promoters known to be differentially hypermethylated in HNSCC in detection of promoterhypermethylation in serum and salivary rinses associated with HNSCC. We did preliminary evaluation via quantitative methylation-specific PCR (Q-MSP) using a panel of 21 genes in a limited cohort of patients with HNSCC and normal controls. Using sensitivity and specificity for individual markers as criteria, we selected panels of eight and six genes, respectively, for use in salivary rinse and serum detection and tested these in an expanded cohort including up to 211 patients with HNSCC and 527 normal controls. Results: Marker panels in salivary rinses showed improved detection when compared with single markers, including a panel with 35% sensitivity and 90% specificity and a panel with 85% sensitivity and 30% specificity. A similar pattern was noted in serum panels, including a panel with 84.5% specificity with 50.0% sensitivity and a panel with sensitivity of 81.0% with specificity of 43.5%. We also noted that serum and salivary rinse compartments showed a differential pattern of methylation in normal subjects that influenced the utility of individual markers. Conclusions: Q-MSP detection of HNSCC in serum and salivary rinses using multiple targets offers improved performance when compared with single markers. Compartment-specific methylation in normal subjects affects the utility of Q-MSP detection strategies.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalClinical Cancer Research
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Body Fluids
Methylation
Serum
Sensitivity and Specificity
Polymerase Chain Reaction
Genetic Association Studies
Tumor Suppressor Genes
Genetic Promoter Regions
Epigenomics
Genes
Carcinoma, squamous cell of head and neck
Research Design
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. / Carvalho, André Lopes; Jeronimo, Carmen; Kim, Michael; Henrique, Rui; Zhang, Zhe; Hoque, Mohammad O.; Chang, Steve; Brait, Mariana; Nayak, Chetan S.; Jiang, Wei Wen; Claybourne, Quia; Tokumaru, Yutaka; Lee, Juna; Goldenberg, David; Garrett-Mayer, Elizabeth; Goodman, Steven; Moon, Chul So; Koch, Wayne; Westra, William H.; Sidransky, David; Califano, Joseph A.

In: Clinical Cancer Research, Vol. 14, No. 1, 01.01.2008, p. 97-107.

Research output: Contribution to journalArticle

Carvalho, AL, Jeronimo, C, Kim, M, Henrique, R, Zhang, Z, Hoque, MO, Chang, S, Brait, M, Nayak, CS, Jiang, WW, Claybourne, Q, Tokumaru, Y, Lee, J, Goldenberg, D, Garrett-Mayer, E, Goodman, S, Moon, CS, Koch, W, Westra, WH, Sidransky, D & Califano, JA 2008, 'Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma', Clinical Cancer Research, vol. 14, no. 1, pp. 97-107. https://doi.org/10.1158/1078-0432.CCR-07-0722
Carvalho, André Lopes ; Jeronimo, Carmen ; Kim, Michael ; Henrique, Rui ; Zhang, Zhe ; Hoque, Mohammad O. ; Chang, Steve ; Brait, Mariana ; Nayak, Chetan S. ; Jiang, Wei Wen ; Claybourne, Quia ; Tokumaru, Yutaka ; Lee, Juna ; Goldenberg, David ; Garrett-Mayer, Elizabeth ; Goodman, Steven ; Moon, Chul So ; Koch, Wayne ; Westra, William H. ; Sidransky, David ; Califano, Joseph A. / Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 1. pp. 97-107.
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abstract = "Purpose: To evaluate aberrant promoter hypermethylation of candidate tumor suppressor genes as a means to detect epigenetic alterations specific to solid tumors, including head and neck squamous cell carcinoma (HNSCC). Experimental Design: Using promoter regions identified via a candidate gene and discovery approach, we evaluated the ability of an expanded panel of CpG-rich promoters known to be differentially hypermethylated in HNSCC in detection of promoterhypermethylation in serum and salivary rinses associated with HNSCC. We did preliminary evaluation via quantitative methylation-specific PCR (Q-MSP) using a panel of 21 genes in a limited cohort of patients with HNSCC and normal controls. Using sensitivity and specificity for individual markers as criteria, we selected panels of eight and six genes, respectively, for use in salivary rinse and serum detection and tested these in an expanded cohort including up to 211 patients with HNSCC and 527 normal controls. Results: Marker panels in salivary rinses showed improved detection when compared with single markers, including a panel with 35{\%} sensitivity and 90{\%} specificity and a panel with 85{\%} sensitivity and 30{\%} specificity. A similar pattern was noted in serum panels, including a panel with 84.5{\%} specificity with 50.0{\%} sensitivity and a panel with sensitivity of 81.0{\%} with specificity of 43.5{\%}. We also noted that serum and salivary rinse compartments showed a differential pattern of methylation in normal subjects that influenced the utility of individual markers. Conclusions: Q-MSP detection of HNSCC in serum and salivary rinses using multiple targets offers improved performance when compared with single markers. Compartment-specific methylation in normal subjects affects the utility of Q-MSP detection strategies.",
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AU - Carvalho, André Lopes

AU - Jeronimo, Carmen

AU - Kim, Michael

AU - Henrique, Rui

AU - Zhang, Zhe

AU - Hoque, Mohammad O.

AU - Chang, Steve

AU - Brait, Mariana

AU - Nayak, Chetan S.

AU - Jiang, Wei Wen

AU - Claybourne, Quia

AU - Tokumaru, Yutaka

AU - Lee, Juna

AU - Goldenberg, David

AU - Garrett-Mayer, Elizabeth

AU - Goodman, Steven

AU - Moon, Chul So

AU - Koch, Wayne

AU - Westra, William H.

AU - Sidransky, David

AU - Califano, Joseph A.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Purpose: To evaluate aberrant promoter hypermethylation of candidate tumor suppressor genes as a means to detect epigenetic alterations specific to solid tumors, including head and neck squamous cell carcinoma (HNSCC). Experimental Design: Using promoter regions identified via a candidate gene and discovery approach, we evaluated the ability of an expanded panel of CpG-rich promoters known to be differentially hypermethylated in HNSCC in detection of promoterhypermethylation in serum and salivary rinses associated with HNSCC. We did preliminary evaluation via quantitative methylation-specific PCR (Q-MSP) using a panel of 21 genes in a limited cohort of patients with HNSCC and normal controls. Using sensitivity and specificity for individual markers as criteria, we selected panels of eight and six genes, respectively, for use in salivary rinse and serum detection and tested these in an expanded cohort including up to 211 patients with HNSCC and 527 normal controls. Results: Marker panels in salivary rinses showed improved detection when compared with single markers, including a panel with 35% sensitivity and 90% specificity and a panel with 85% sensitivity and 30% specificity. A similar pattern was noted in serum panels, including a panel with 84.5% specificity with 50.0% sensitivity and a panel with sensitivity of 81.0% with specificity of 43.5%. We also noted that serum and salivary rinse compartments showed a differential pattern of methylation in normal subjects that influenced the utility of individual markers. Conclusions: Q-MSP detection of HNSCC in serum and salivary rinses using multiple targets offers improved performance when compared with single markers. Compartment-specific methylation in normal subjects affects the utility of Q-MSP detection strategies.

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