Journal article
Fundamental Differences in Cell Cycle Deregulation in Human Papillomavirus–Positive and Human Papillomavirus–Negative Head/Neck and Cervical Cancers
Cancer research (Chicago, Ill.), Vol.67(10), pp.4605-4619
05/15/2007
DOI: 10.1158/0008-5472.CAN-06-3619
PMCID: PMC2858285
PMID: 17510386
Abstract
Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV
+
HNCs and cervical cancers differed in their patterns of gene expression yet shared many changes compared with HPV
−
HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV
+
HNCs and cervical cancers were found to be up-regulated in their expression of a distinct and larger subset of cell cycle genes than that observed in HPV
−
HNC. Moreover, HPV
+
cancers overexpressed testis-specific genes that are normally expressed only in meiotic cells. Many, although not all, of the hallmark differences between HPV
+
HNC and HPV
−
HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testis-specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV
+
and HPV
−
cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV
+
cancers.
Details
- Title: Subtitle
- Fundamental Differences in Cell Cycle Deregulation in Human Papillomavirus–Positive and Human Papillomavirus–Negative Head/Neck and Cervical Cancers
- Creators
- Dohun Pyeon - McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WisconsinMichael A Newton - Department of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WisconsinPaul F Lambert - McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WisconsinJohan A den Boon - McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WisconsinSrikumar Sengupta - McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WisconsinCarmen J Marsit - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MassachusettsCraig D Woodworth - Department of Biology, Clarkson University, Potsdam, New YorkJoseph P Connor - Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WisconsinThomas H Haugen - Department of Pathology, Veterans Affairs Medical Center, University of Iowa, Iowa City, IowaElaine M Smith - Department of Epidemiology, University of Iowa, Iowa City, IowaKarl T Kelsey - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MassachusettsLubomir P Turek - Department of Pathology, Veterans Affairs Medical Center, University of Iowa, Iowa City, IowaPaul Ahlquist - McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.67(10), pp.4605-4619
- DOI
- 10.1158/0008-5472.CAN-06-3619
- PMID
- 17510386
- PMCID
- PMC2858285
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 05/15/2007
- Academic Unit
- Epidemiology; Pathology
- Record Identifier
- 9984047989602771
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