title: True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.
abstract: Squamous lung carcinoma lacks specific "ad hoc" therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed ≥8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3) showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly "amplified for chromosome 3q" when showing ≥8 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.
authors.affiliation: ISH Molecular Lab, Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy. matteo.brunelli@univr.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.forename: Sara
authors.initials: S
authors.lastname: Cingarlini
authors.forename: Francesca
authors.initials: F
authors.lastname: Simionato
authors.forename: Anna
authors.initials: A
authors.lastname: Caliò
authors.forename: Albino
authors.initials: A
authors.lastname: Eccher
authors.forename: Claudia
authors.initials: C
authors.lastname: Parolini
authors.forename: Antonio
authors.initials: A
authors.lastname: Iannucci
authors.forename: Eliana
authors.initials: E
authors.lastname: Gilioli
authors.forename: Serena
authors.initials: S
authors.lastname: Pedron
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Ioana
authors.initials: I
authors.lastname: Borze
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
authors.forename: Stefano
authors.initials: S
authors.lastname: Gobbo
authors.forename: Antonio
authors.initials: A
authors.lastname: Santo
authors.forename: Luca
authors.initials: L
authors.lastname: Tondulli
authors.forename: Francesco
authors.initials: F
authors.lastname: Calabrò
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D058674:Chromosome Duplication; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology