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Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection

Recently increasing high-risk HPV+ OSCC exhibits unique clinical and molecular characteristics compared to HPV-unrelated (HPV−) counterpart. Genomic copy number variations (CNVs), unique in HPV+ OSCCs, and their role for the prognosis prediction remains poorly studied. Here, we analyzed the distinct...

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Autores principales: Rhie, Arang, Park, Weon Seo, Choi, Moon Kyung, Kim, Ji-Hyun, Ryu, Junsun, Ryu, Chang Hwan, Kim, Jong-Il, Jung, Yuh-Seog
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058900/
https://www.ncbi.nlm.nih.gov/pubmed/26683928
http://dx.doi.org/10.1097/MD.0000000000002187
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author Rhie, Arang
Park, Weon Seo
Choi, Moon Kyung
Kim, Ji-Hyun
Ryu, Junsun
Ryu, Chang Hwan
Kim, Jong-Il
Jung, Yuh-Seog
author_facet Rhie, Arang
Park, Weon Seo
Choi, Moon Kyung
Kim, Ji-Hyun
Ryu, Junsun
Ryu, Chang Hwan
Kim, Jong-Il
Jung, Yuh-Seog
author_sort Rhie, Arang
collection PubMed
description Recently increasing high-risk HPV+ OSCC exhibits unique clinical and molecular characteristics compared to HPV-unrelated (HPV−) counterpart. Genomic copy number variations (CNVs), unique in HPV+ OSCCs, and their role for the prognosis prediction remains poorly studied. Here, we analyzed the distinct genomic copy number variations (CNVs) in human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OSCC) and their role as a prognosticator after curative resection. For 58 consecutive, Korean OSCC patients that underwent surgery-based treatment with median 10 years of follow-up, HPV-related markers, and genome-wide CNV analysis were analyzed. Clinical associations between the CNV profile and survival analyses were followed. p16 expression predicted the overall survival (OS) (hazard ratio [HR] = 0.27, confidence interval [CI]: 0.39–0.80, P = 0.0006) better than HPV L1 PCR (HR = 0.83, CI: 0.66–1.29, P = 0.64), smoking, or other variables. Although the overall number of CNVs was not significantly different, 30 loci showed unique CNV patterns between the p16(+) and p16− groups. A region containing PRDM2 was amplified only in the p16(+) group, whereas EGFR and 11q13.3 showed increased amplification in p16− counterpart. Loss of a locus containing FGF18 led to a worse, but gain of region including CDK10 and RAD18 led to better overall survival (OS) in all OSCC patients. Meanwhile, subgroup analysis of p16(+) OSCC revealed that amplification of regions harboring HRAS and loss of locus bearing KDR led to better OS. p16(+) OSCC exhibit distinct CNV patterns compared with p16− counterpart. Specific patterns of CNVs predict better survival, especially in p16(+) OSCC. This might allow better insights of the outcome after curative resection for HPV+ and HPV− OSCC.
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spelling pubmed-50589002016-11-01 Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection Rhie, Arang Park, Weon Seo Choi, Moon Kyung Kim, Ji-Hyun Ryu, Junsun Ryu, Chang Hwan Kim, Jong-Il Jung, Yuh-Seog Medicine (Baltimore) 6000 Recently increasing high-risk HPV+ OSCC exhibits unique clinical and molecular characteristics compared to HPV-unrelated (HPV−) counterpart. Genomic copy number variations (CNVs), unique in HPV+ OSCCs, and their role for the prognosis prediction remains poorly studied. Here, we analyzed the distinct genomic copy number variations (CNVs) in human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OSCC) and their role as a prognosticator after curative resection. For 58 consecutive, Korean OSCC patients that underwent surgery-based treatment with median 10 years of follow-up, HPV-related markers, and genome-wide CNV analysis were analyzed. Clinical associations between the CNV profile and survival analyses were followed. p16 expression predicted the overall survival (OS) (hazard ratio [HR] = 0.27, confidence interval [CI]: 0.39–0.80, P = 0.0006) better than HPV L1 PCR (HR = 0.83, CI: 0.66–1.29, P = 0.64), smoking, or other variables. Although the overall number of CNVs was not significantly different, 30 loci showed unique CNV patterns between the p16(+) and p16− groups. A region containing PRDM2 was amplified only in the p16(+) group, whereas EGFR and 11q13.3 showed increased amplification in p16− counterpart. Loss of a locus containing FGF18 led to a worse, but gain of region including CDK10 and RAD18 led to better overall survival (OS) in all OSCC patients. Meanwhile, subgroup analysis of p16(+) OSCC revealed that amplification of regions harboring HRAS and loss of locus bearing KDR led to better OS. p16(+) OSCC exhibit distinct CNV patterns compared with p16− counterpart. Specific patterns of CNVs predict better survival, especially in p16(+) OSCC. This might allow better insights of the outcome after curative resection for HPV+ and HPV− OSCC. Wolters Kluwer Health 2015-12-18 /pmc/articles/PMC5058900/ /pubmed/26683928 http://dx.doi.org/10.1097/MD.0000000000002187 Text en Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
spellingShingle 6000
Rhie, Arang
Park, Weon Seo
Choi, Moon Kyung
Kim, Ji-Hyun
Ryu, Junsun
Ryu, Chang Hwan
Kim, Jong-Il
Jung, Yuh-Seog
Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection
title Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection
title_full Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection
title_fullStr Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection
title_full_unstemmed Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection
title_short Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection
title_sort genomic copy number variations characterize the prognosis of both p16-positive and p16-negative oropharyngeal squamous cell carcinoma after curative resection
topic 6000
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058900/
https://www.ncbi.nlm.nih.gov/pubmed/26683928
http://dx.doi.org/10.1097/MD.0000000000002187
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