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Gene expression profiles in HPV-infected head and neck cancer.
J Pathol. 2007 Nov; 213(3):283-93.JP

Abstract

Epidemiological and laboratory evidence indicate that, in addition to tobacco and alcohol, human papillomaviruses (HPV) play an important aetiological role in a subset of head and neck squamous cell carcinoma (HNSCC). To evaluate the molecular pathogenesis of HPV-infected HNSCC, we compared gene expression patterns between HPV-positive and -negative HNSCC tumours using cDNA microarrays. Tumour tissue was collected from 42 histologically confirmed HNSCC patients from an inner-city area of New York. Total DNA and RNA were extracted and purified from frozen tumour samples and gene expression levels were compared to a universal human reference RNA standard using a 27 323 cDNA microarray chip. HPV detection and genotyping were performed using an MY09/11-PCR system and RT-PCR. HPV was detected in 29% of HNSCC tumours. Most harboured only HPV16 and expressed the HPV16-E6 oncogene. HPV prevalence was highest in pharyngeal tumours (45%). Gene expression patterns that differentiated HPV-positive from negative tumours were compared by supervised classification analysis, and a multiple-gene signature was found to predict HPV16 prevalence in primary HNSCC with a false discovery rate < 0.2. Focusing on never-smokers, we further identified a distinct subset of 123 genes that were specifically dysregulated in HPV16-positive HNSCC. Overexpressed genes in HPV-positive HNSCC tumours included the retinoblastoma-binding protein (p18), replication factor-C gene, and an E2F-dimerization partner transcription factor (TFDP2) that have also been found to be overexpressed in cervical cancer. An additional subset of genes involved in viral defence and immune response, including interleukins and interferon-induced proteins, was found to be down-regulated in HPV-positive tumours, supporting a characteristic and unique transcriptional profile in HPV-induced HNSCC.

Authors+Show Affiliations

Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. nschlech@aecom.yu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17893858

Citation

Schlecht, N F., et al. "Gene Expression Profiles in HPV-infected Head and Neck Cancer." The Journal of Pathology, vol. 213, no. 3, 2007, pp. 283-93.
Schlecht NF, Burk RD, Adrien L, et al. Gene expression profiles in HPV-infected head and neck cancer. J Pathol. 2007;213(3):283-93.
Schlecht, N. F., Burk, R. D., Adrien, L., Dunne, A., Kawachi, N., Sarta, C., Chen, Q., Brandwein-Gensler, M., Prystowsky, M. B., Childs, G., Smith, R. V., & Belbin, T. J. (2007). Gene expression profiles in HPV-infected head and neck cancer. The Journal of Pathology, 213(3), 283-93.
Schlecht NF, et al. Gene Expression Profiles in HPV-infected Head and Neck Cancer. J Pathol. 2007;213(3):283-93. PubMed PMID: 17893858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene expression profiles in HPV-infected head and neck cancer. AU - Schlecht,N F, AU - Burk,R D, AU - Adrien,L, AU - Dunne,A, AU - Kawachi,N, AU - Sarta,C, AU - Chen,Q, AU - Brandwein-Gensler,M, AU - Prystowsky,M B, AU - Childs,G, AU - Smith,R V, AU - Belbin,T J, PY - 2007/9/26/pubmed PY - 2007/12/8/medline PY - 2007/9/26/entrez SP - 283 EP - 93 JF - The Journal of pathology JO - J. Pathol. VL - 213 IS - 3 N2 - Epidemiological and laboratory evidence indicate that, in addition to tobacco and alcohol, human papillomaviruses (HPV) play an important aetiological role in a subset of head and neck squamous cell carcinoma (HNSCC). To evaluate the molecular pathogenesis of HPV-infected HNSCC, we compared gene expression patterns between HPV-positive and -negative HNSCC tumours using cDNA microarrays. Tumour tissue was collected from 42 histologically confirmed HNSCC patients from an inner-city area of New York. Total DNA and RNA were extracted and purified from frozen tumour samples and gene expression levels were compared to a universal human reference RNA standard using a 27 323 cDNA microarray chip. HPV detection and genotyping were performed using an MY09/11-PCR system and RT-PCR. HPV was detected in 29% of HNSCC tumours. Most harboured only HPV16 and expressed the HPV16-E6 oncogene. HPV prevalence was highest in pharyngeal tumours (45%). Gene expression patterns that differentiated HPV-positive from negative tumours were compared by supervised classification analysis, and a multiple-gene signature was found to predict HPV16 prevalence in primary HNSCC with a false discovery rate < 0.2. Focusing on never-smokers, we further identified a distinct subset of 123 genes that were specifically dysregulated in HPV16-positive HNSCC. Overexpressed genes in HPV-positive HNSCC tumours included the retinoblastoma-binding protein (p18), replication factor-C gene, and an E2F-dimerization partner transcription factor (TFDP2) that have also been found to be overexpressed in cervical cancer. An additional subset of genes involved in viral defence and immune response, including interleukins and interferon-induced proteins, was found to be down-regulated in HPV-positive tumours, supporting a characteristic and unique transcriptional profile in HPV-induced HNSCC. SN - 0022-3417 UR - https://www.unboundmedicine.com/medline/citation/17893858/Gene_expression_profiles_in_HPV_infected_head_and_neck_cancer_ L2 - https://doi.org/10.1002/path.2227 DB - PRIME DP - Unbound Medicine ER -