title: DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes.
abstract: 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.
authors.affiliation: Bart's Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, John Vane Science Centre, Charterhouse square, London, United Kingdom.
authors.forename: Susannah
authors.initials: S
authors.lastname: La-Touche
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lemetre
authors.affiliation: Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
authors.forename: Maryou
authors.initials: M
authors.lastname: Lambros
authors.affiliation: Bart's Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, John Vane Science Centre, Charterhouse square, London, United Kingdom.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stankiewicz
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Charlotte K Y
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.affiliation: St George's Hospital, Tooting, London, United Kingdom.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Rajab
authors.affiliation: St George's Hospital, Tooting, London, United Kingdom.
authors.forename: Brendan
authors.initials: B
authors.lastname: Tinwell
authors.affiliation: St George's Hospital, Tooting, London, United Kingdom.
authors.forename: Cathy
authors.initials: C
authors.lastname: Corbishley
authors.affiliation: St George's Hospital, Tooting, London, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Watkin
authors.affiliation: Bart's Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, John Vane Science Centre, Charterhouse square, London, United Kingdom.
authors.forename: Dan
authors.initials: D
authors.lastname: Berney
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.|Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D055028:Comparative Genomic Hybridization / Q000379:methods; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D008297:Male; D010412:Penile Neoplasms / Q000235:genetics* / Q000821:virology*