DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver GenesReportar como inadecuado




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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.



Autor: Susannah La-Touche , Christophe Lemetre , Maryou Lambros, Elzbieta Stankiewicz, Charlotte K. Y. Ng, Britta Weigelt, Ramzi Rajab,

Fuente: http://plos.srce.hr/



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