True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.

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 v...

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Autores principales: Matteo Brunelli, Emilio Bria, Alessia Nottegar, Sara Cingarlini, Francesca Simionato, Anna Caliò, Albino Eccher, Claudia Parolini, Antonio Iannucci, Eliana Gilioli, Serena Pedron, Francesco Massari, Giampaolo Tortora, Ioana Borze, Sakari Knuutila, Stefano Gobbo, Antonio Santo, Luca Tondulli, Francesco Calabrò, Guido Martignoni, Marco Chilosi
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/c836151bf57a4429b7a03c2bb3ae5354
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spelling oai:doaj.org-article:c836151bf57a4429b7a03c2bb3ae53542021-11-18T08:06:10ZTrue 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.1932-620310.1371/journal.pone.0049689https://doaj.org/article/c836151bf57a4429b7a03c2bb3ae53542012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23236352/?tool=EBIhttps://doaj.org/toc/1932-6203Squamous 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.Matteo BrunelliEmilio BriaAlessia NottegarSara CingarliniFrancesca SimionatoAnna CaliòAlbino EccherClaudia ParoliniAntonio IannucciEliana GilioliSerena PedronFrancesco MassariGiampaolo TortoraIoana BorzeSakari KnuutilaStefano GobboAntonio SantoLuca TondulliFrancesco CalabròGuido MartignoniMarco ChilosiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e49689 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Matteo Brunelli
Emilio Bria
Alessia Nottegar
Sara Cingarlini
Francesca Simionato
Anna Caliò
Albino Eccher
Claudia Parolini
Antonio Iannucci
Eliana Gilioli
Serena Pedron
Francesco Massari
Giampaolo Tortora
Ioana Borze
Sakari Knuutila
Stefano Gobbo
Antonio Santo
Luca Tondulli
Francesco Calabrò
Guido Martignoni
Marco Chilosi
True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.
description 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.
format article
author Matteo Brunelli
Emilio Bria
Alessia Nottegar
Sara Cingarlini
Francesca Simionato
Anna Caliò
Albino Eccher
Claudia Parolini
Antonio Iannucci
Eliana Gilioli
Serena Pedron
Francesco Massari
Giampaolo Tortora
Ioana Borze
Sakari Knuutila
Stefano Gobbo
Antonio Santo
Luca Tondulli
Francesco Calabrò
Guido Martignoni
Marco Chilosi
author_facet Matteo Brunelli
Emilio Bria
Alessia Nottegar
Sara Cingarlini
Francesca Simionato
Anna Caliò
Albino Eccher
Claudia Parolini
Antonio Iannucci
Eliana Gilioli
Serena Pedron
Francesco Massari
Giampaolo Tortora
Ioana Borze
Sakari Knuutila
Stefano Gobbo
Antonio Santo
Luca Tondulli
Francesco Calabrò
Guido Martignoni
Marco Chilosi
author_sort Matteo Brunelli
title True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.
title_short True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.
title_full True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.
title_fullStr True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.
title_full_unstemmed True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.
title_sort true 3q chromosomal amplification in squamous cell lung carcinoma by fish and acgh molecular analysis: impact on targeted drugs.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/c836151bf57a4429b7a03c2bb3ae5354
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