title: Loss of heterozygosity and copy number alterations in flow-sorted bulky cervical cancer.
abstract: Treatment choices for cervical cancer are primarily based on clinical FIGO stage and the post-operative evaluation of prognostic parameters including tumor diameter, parametrial and lymph node involvement, vaso-invasion, infiltration depth, and histological type. The aim of this study was to evaluate genomic changes in bulky cervical tumors and their relation to clinical parameters, using single nucleotide polymorphism (SNP)-analysis. Flow-sorted tumor cells and patient-matched normal cells were extracted from 81 bulky cervical tumors. DNA-index (DI) measurement and whole genome SNP-analysis were performed. Data were analyzed to detect copy number alterations (CNA) and allelic balance state: balanced, imbalanced or pure LOH, and their relation to clinical parameters. The DI varied from 0.92-2.56. Pure LOH was found in ≥40% of samples on chromosome-arms 3p, 4p, 6p, 6q, and 11q, CN gains in >20% on 1q, 3q, 5p, 8q, and 20q, and losses on 2q, 3p, 4p, 11q, and 13q. Over 40% showed gain on 3q. The only significant differences were found between histological types (squamous, adeno and adenosquamous) in the lesser allele intensity ratio (LAIR) (p = 0.035) and in the CNA analysis (p = 0.011). More losses were found on chromosome-arm 2q (FDR = 0.004) in squamous tumors and more gains on 7p, 7q, and 9p in adenosquamous tumors (FDR = 0.006, FDR = 0.004, and FDR = 0.029). Whole genome analysis of bulky cervical cancer shows widespread changes in allelic balance and CN. The overall genetic changes and CNA on specific chromosome-arms differed between histological types. No relation was found with the clinical parameters that currently dictate treatment choice.
authors.affiliation: Leiden University Medical Center, Department of Gynecology, Leiden, The Netherlands. s.a.h.m.van_den_tillaart@lumc.nl
authors.forename: Sabrina A H M
authors.initials: SA
authors.lastname: van den Tillaart
authors.forename: Wim E
authors.initials: WE
authors.lastname: Corver
authors.forename: Dina
authors.initials: D
authors.lastname: Ruano Neto
authors.forename: Natalja T
authors.initials: NT
authors.lastname: ter Haar
authors.forename: Jelle J
authors.initials: JJ
authors.lastname: Goeman
authors.forename: J Baptist M Z
authors.initials: JB
authors.lastname: Trimbos
authors.forename: Gertjan J
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: Jan
authors.initials: J
authors.lastname: Oosting
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology