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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

Genomic coordinates of A. losses at chromosome 13 and B. gains at chromosome 20 are shown for all hrHPV-positive carcinomas. Chromosomal alterations in CxSCCs are shown by dashed lines and alterations in hrHPV-positive HNSCCs by solid lines. In C. the smallest regions of overlap (SROs) between hrHPV-positive carcinomas at chromosome 13 and 20 are summarised.
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Figure 4: Genomic coordinates of A. losses at chromosome 13 and B. gains at chromosome 20 are shown for all hrHPV-positive carcinomas. Chromosomal alterations in CxSCCs are shown by dashed lines and alterations in hrHPV-positive HNSCCs by solid lines. In C. the smallest regions of overlap (SROs) between hrHPV-positive carcinomas at chromosome 13 and 20 are summarised.

Mentions: As described above gain at 20p12.1-q13.33 and loss at 13q21.1-21.33 were significantly more frequent in hrHPV-positive SCCs compared to hrHPV-negative ones. In fact, a 4.5 megabase (Mb) region on chromosome 20 (20q11.21-q11.23), and a 2 Mb region on chromosome 13 (13q21.1) formed the smallest regions of overlap (SRO) at these respective loci when all hrHPV-positive carcinomas were considered (Figure 4A and 4B). The SRO at chromosome 20q contains 78 genes and the one at chromosome 13q contains 6 genes [see Additional file 1]. Within the SRO at chromosome 20, two genes reside, i.e. NCOA6 and RBM39, which showed elevated expression in hrHPV16 E7 expressing cells in vitro [20]. Other cancer-related genes located within this SRO include PIGU, E2F1, and DNMT3B. The SRO on chromosome 13 encompasses the PCDH17 gene and a cluster of five identical loci all of which are predicted to encode proline-rich proteins that contain several dopamine D4 receptor signatures.


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)

Genomic coordinates of A. losses at chromosome 13 and B. gains at chromosome 20 are shown for all hrHPV-positive carcinomas. Chromosomal alterations in CxSCCs are shown by dashed lines and alterations in hrHPV-positive HNSCCs by solid lines. In C. the smallest regions of overlap (SROs) between hrHPV-positive carcinomas at chromosome 13 and 20 are summarised.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Genomic coordinates of A. losses at chromosome 13 and B. gains at chromosome 20 are shown for all hrHPV-positive carcinomas. Chromosomal alterations in CxSCCs are shown by dashed lines and alterations in hrHPV-positive HNSCCs by solid lines. In C. the smallest regions of overlap (SROs) between hrHPV-positive carcinomas at chromosome 13 and 20 are summarised.
Mentions: As described above gain at 20p12.1-q13.33 and loss at 13q21.1-21.33 were significantly more frequent in hrHPV-positive SCCs compared to hrHPV-negative ones. In fact, a 4.5 megabase (Mb) region on chromosome 20 (20q11.21-q11.23), and a 2 Mb region on chromosome 13 (13q21.1) formed the smallest regions of overlap (SRO) at these respective loci when all hrHPV-positive carcinomas were considered (Figure 4A and 4B). The SRO at chromosome 20q contains 78 genes and the one at chromosome 13q contains 6 genes [see Additional file 1]. Within the SRO at chromosome 20, two genes reside, i.e. NCOA6 and RBM39, which showed elevated expression in hrHPV16 E7 expressing cells in vitro [20]. Other cancer-related genes located within this SRO include PIGU, E2F1, and DNMT3B. The SRO on chromosome 13 encompasses the PCDH17 gene and a cluster of five identical loci all of which are predicted to encode proline-rich proteins that contain several dopamine D4 receptor signatures.

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