Abstract
BackgroundIt is well known that a persistent infection with high-risk human papillomavirus (hrHPV) is causally involved in the development of squamous cell carcinomas of the uterine cervix (CxSCCs) and a subset of SCCs of the head and neck (HNSCCs). The latter differ from hrHPV-negative HNSCCs at the clinical and molecular level.MethodsTo determine whether hrHPV-associated SCCs arising from different organs have specific chromosomal alterations in common, we compared genome-wide chromosomal profiles of 10 CxSCCs (all hrHPV-positive) with 12 hrHPV-positive HNSCCs and 30 hrHPV-negative HNSCCs. Potential organ-specific alterations and alterations shared by SCCs in general were investigated as well.ResultsUnsupervised hierarchical clustering resulted in one mainly hrHPV-positive and one mainly hrHPV-negative cluster. Interestingly, loss at 13q and gain at 20q were frequent in HPV-positive carcinomas of both origins, but uncommon in hrHPV-negative HNSCCs, indicating that these alterations are associated with hrHPV-mediated carcinogenesis. Within the group of hrHPV-positive carcinomas, HNSCCs more frequently showed gains of multiple regions at 8q whereas CxSCCs more often showed loss at 17p. Finally, gains at 3q24-29 and losses at 11q22.3-25 were frequent (>50%) in all sample groups.ConclusionIn this study hrHPV-specific, organ-specific, and pan-SCC chromosomal alterations were identified. The existence of hrHPV-specific alterations in SCCs of different anatomical origin, suggests that these alterations are crucial for hrHPV-mediated carcinogenesis.
Highlights
It is well known that a persistent infection with high-risk human papillomavirus is causally involved in the development of squamous cell carcinomas of the uterine cervix (CxSCCs) and a subset of SCCs of the head and neck (HNSCCs)
In a previous study, using array comparative genomic hybridisation (CGH), we identified a number of chromosomal alterations specific for hrHPVnegative head and neck squamous cell carcinoma (HNSCC) that were absent in high-risk human papillomavirus (hrHPV)-positive HNSCCs, including loss at 3p, 5q, and 9p, and amplifications at 11q [13]
This method enabled us to determine in an unbiased manner whether chromosomal profiles of hrHPV-positive HNSCCs were more closely related to hrHPV-negative HNSCCs or hrHPV-positive squamous cell carcinoma of the uterine cervix (CxSCC)
Summary
It is well known that a persistent infection with high-risk human papillomavirus (hrHPV) is causally involved in the development of squamous cell carcinomas of the uterine cervix (CxSCCs) and a subset of SCCs of the head and neck (HNSCCs). The latter differ from hrHPVnegative HNSCCs at the clinical and molecular level. HrHPV is present in virtually all cervical carcinomas and the viral oncogenes E6 and E7 are consistently expressed in cervical cancers and precancers Deregulated expression of these oncogenes in the basal, dividing cells of the epithelium interferes with cell cycle control due to their ability to induce degradation of the tumour suppressor proteins p53 and pRb, respectively. The necessity of these and other additional (epi)genetic alterations in the carcinogenic process is illustrated by the fact that their frequency increases with increasing severity of cervical disease
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