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Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck.

Wilting SM, Smeets SJ, Snijders PJ, van Wieringen WN, van de Wiel MA, Meijer GA, Ylstra B, Leemans CR, Meijer CJ, Brakenhoff RH, Braakhuis BJ, Steenbergen RD - BMC Med Genomics (2009)

Bottom Line: Unsupervised hierarchical clustering resulted in one mainly hrHPV-positive and one mainly hrHPV-negative cluster.In 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. s.wilting@vumc.nl

ABSTRACT

Background: 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 hrHPV-negative HNSCCs at the clinical and molecular level.

Methods: To 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.

Results: Unsupervised 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.

Conclusion: In 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.

No MeSH data available.


Related in: MedlinePlus

Result from the unsupervised hierarchical clustering analysis. Cluster 1 contains in majority hrHPV-positive carcinomas, as is indicated by the black boxes in the legend underneath the heatmap (p < 0.0001).
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Figure 1: Result from the unsupervised hierarchical clustering analysis. Cluster 1 contains in majority hrHPV-positive carcinomas, as is indicated by the black boxes in the legend underneath the heatmap (p < 0.0001).

Mentions: As is shown in Figure 1, two clusters emerged. Cluster 1 contained 24 samples, 18 of which were hrHPV-positive (75%) and 6 were hrHPV-negative. Cluster 2 contained 28 samples of which 4 samples were hrHPV-positive and 24 were hrHPV-negative (86%). This association between cluster assignment and hrHPV status was statistically significant (p < 0.0001). The hrHPV-positive cluster 1 included both samples of cervical (n = 8) and head and neck origin (n = 10), indicating similarities between the chromosomal profiles of hrHPV-induced carcinomas of different anatomical origins. Within cluster 1, however, 7 out of 8 cervical samples formed a separate sub-cluster. This suggests that organ-specific alterations exist as well in hrHPV-positive HNSCCs and CxSCCs.


Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck.

Wilting SM, Smeets SJ, Snijders PJ, van Wieringen WN, van de Wiel MA, Meijer GA, Ylstra B, Leemans CR, Meijer CJ, Brakenhoff RH, Braakhuis BJ, Steenbergen RD - BMC Med Genomics (2009)

Result from the unsupervised hierarchical clustering analysis. Cluster 1 contains in majority hrHPV-positive carcinomas, as is indicated by the black boxes in the legend underneath the heatmap (p < 0.0001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698908&req=5

Figure 1: Result from the unsupervised hierarchical clustering analysis. Cluster 1 contains in majority hrHPV-positive carcinomas, as is indicated by the black boxes in the legend underneath the heatmap (p < 0.0001).
Mentions: As is shown in Figure 1, two clusters emerged. Cluster 1 contained 24 samples, 18 of which were hrHPV-positive (75%) and 6 were hrHPV-negative. Cluster 2 contained 28 samples of which 4 samples were hrHPV-positive and 24 were hrHPV-negative (86%). This association between cluster assignment and hrHPV status was statistically significant (p < 0.0001). The hrHPV-positive cluster 1 included both samples of cervical (n = 8) and head and neck origin (n = 10), indicating similarities between the chromosomal profiles of hrHPV-induced carcinomas of different anatomical origins. Within cluster 1, however, 7 out of 8 cervical samples formed a separate sub-cluster. This suggests that organ-specific alterations exist as well in hrHPV-positive HNSCCs and CxSCCs.

Bottom Line: Unsupervised hierarchical clustering resulted in one mainly hrHPV-positive and one mainly hrHPV-negative cluster.In 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. s.wilting@vumc.nl

ABSTRACT

Background: 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 hrHPV-negative HNSCCs at the clinical and molecular level.

Methods: To 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.

Results: Unsupervised 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.

Conclusion: In 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.

No MeSH data available.


Related in: MedlinePlus