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• W2740124416 abstract "Urothelial carcinomas (UC) are characterized, among other aberrations, by chromosome 3, 7, 17 gains and 9p21 (p16) loss. Since UC cells readily exfoliate into the urine, molecular cytogenetics techniques have been used to detect cells consistent with UC diagnosis and follow-up: a multitarget Fluorescence In Situ Hybridization (FISH) test, composed of 3, 7 and 17 centromeres and 9p21 locus multicolor probes, has been proved useful for atypical cells identification in both void urine and lower and upper urinary tract samples before morphological changes are apparent through cytological and histological examination. To date, there are no uniform criteria for urine FISH scoring though the test is commonly considered positive following the UroVysion Bladder Cancer Kit criteria (Abbott Molecular): 4 or more cells with a gain of 2 or more chromosomes (polysomy), and/or 12 or more cells with 9p21 homozygous deletion. This definition of polysomy includes trisomy and tetrasomy classes, but, as tetraploidy may represent cells at S/G2 phase, this criterion may lead to false-positives; moreover it has been described that also inflammation induces tetraploidy, and that small percentages of normal urine cells show trisomy/tetrasomy. On the other hand, triploidy and tetraploidy may have a direct role in tumorigenesis, as an intermediate state in the development of cancer aneuploidy. At the moment little is reported about the clinical correlations of urine FISH cases showing only trisomy/tetrasomy and more data are needed to clarify the diagnostic value of triploid and tetraploid urothelial cells. Aiming to better classify patients with a trisomy/tetrasomy urine FISH result, we extracted genomic DNA from 50 fixed urine cell suspensions, previously tested by urine FISH, and investigated them for the presence of fibroblast growth factor receptor 3 (FGFR3) and telomerase reverse transcriptase (TERT) promoter mutations, which constitute the most recurrent somatic alterations in BC. In particular frequent mutations in exons 7, 10 and 15 of FGFR3 characterize non-muscle invasive UC while mutations in the core promoter region of TERT gene, mainly at -124 and -146 positions from the ATG start site, have emerged as the most frequent somatic genetic alteration in both non-muscle invasive and muscle invasive UC. All specimens were subjected to PCR amplification and Sanger sequencing for FGFR3 exon 7 and 10, and for the C228T and C250T TERT promoter mutations. A preliminary analysis of 20 urine FISH cases showed 4 samples with trisomy/tetrasomy, and 1 of these 4 had a mutation of the TERT promotor. Complete results of the FGFR3 and TERT promoter molecular analysis will be presented and correlated to both FISH results and patients clinical data, in order to evaluate if the presence of FGFR3 and/or TERT promoter mutations in urine samples with FISH detected trisomy/tetrasomy may help to identify patients with a higher risk of recurrence and progression. Citation Format: Lorenza Pecciarini, Valeria De Pascali, Ilaria Francaviglia, Anna Talarico, Chiara Iacona, Massimo Freschi, Maria Giulia Cangi, Claudio Doglioni. Molecular characterization of triploid and tetraploid urine FISH samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 756. doi:10.1158/1538-7445.AM2017-756" @default.
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• W2740124416 date "2017-07-01" @default.
• W2740124416 modified "2023-09-25" @default.
• W2740124416 title "Abstract 756: Molecular characterization of triploid and tetraploid urine FISH samples" @default.
• W2740124416 doi "https://doi.org/10.1158/1538-7445.am2017-756" @default.
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