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dc.date.accessioned2018-07-05T09:28:12Z
dc.date.issued2016
dc.identifierhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146740
dc.identifier.citationPLOS ONE, 2016, 11 (2)
dc.identifier.issn1932-6203
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1987
dc.description.abstractPenile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents.
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectSQUAMOUS-CELL CARCINOMA COMPARATIVE GENOMIC HYBRIDIZATION LYMPH-NODE METASTASIS HPV INFECTION DUCTAL CARCINOMAS BREAST CANCERS P53 ACTIVATION EXPRESSION RESOLUTION
dc.titleDNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes
dc.typeJournal Article
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPLOS ONE
pubs.issue2
pubs.notesISI Document Delivery No.: DF3VL Times Cited: 0 Cited Reference Count: 50 La-Touche, Susannah Lemetre, Christophe Lambros, Maryou Stankiewicz, Elzbieta Ng, Charlotte K. Y. Weigelt, Britta Rajab, Ramzi Tinwell, Brendan Corbishley, Cathy Watkin, Nick Berney, Dan Reis-Filho, Jorge S. Orchid male cancer charity; Barts Cancer Institute (London); Queen Mary University of London; St Georges Hospital (London); Memorial Sloan Kettering Cancer Center (New York); Institute of Cancer Research (London); [ONAG1R1R] This work was financially supported by Orchid male cancer charity [https://www.orchid-cancer.org.uk], including some equipment, supplies and reimbursement for attending the 29th Annual European Association of Urology Congress. The grant code for internal use at Queen Mary, University of London was ONAG1R1R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Collaborative support was provided by Barts Cancer Institute (London), Queen Mary University of London, St Georges Hospital (London), Memorial Sloan Kettering Cancer Center (New York) and the Institute of Cancer Research (London). 0 PUBLIC LIBRARY SCIENCE SAN FRANCISCO PLOS ONE public Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents.
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.volume11
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
dc.contributor.icrauthorLambros, Maryouen


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