1. True 3q Chromosomal Amplification in Squamous Cell Lung Carcinoma by FISH and aCGH Molecular Analysis: Impact on Targeted Drugs
- Author
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Alessia Nottegar, Serena Pedron, Matteo Brunelli, Claudia Parolini, Giampaolo Tortora, F. Calabrò, Eliana Gilioli, Luca Tondulli, Emilio Bria, Antonio Iannucci, Albino Eccher, Francesco Massari, Sara Cingarlini, Ioana Borze, Francesca Simionato, Marco Chilosi, Antonio Santo, Anna Caliò, Guido Martignoni, Stefano Gobbo, Sakari Knuutila, Haartman Institute (-2014), and Department of Pathology
- Subjects
Lung Neoplasms ,SOX2 ,Biology ,Squamous lung carcinoma ,3q Chromosomal Amplification ,Squamous Cell Lung Carcinoma ,Lung and Intrathoracic Tumors ,Chromosomal Disorders ,0302 clinical medicine ,Molecular Cell Biology ,Chromosome Duplication ,Pathology ,COMPARATIVE GENOMIC HYBRIDIZATION ,In Situ Hybridization, Fluorescence ,0303 health sciences ,Multidisciplinary ,CHEMOTHERAPY ,CANCER ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Chromosomal region ,Carcinoma, Squamous Cell ,SURVIVAL ,Adenocarcinoma ,Medicine ,Chromosomes, Human, Pair 3 ,Molecular Pathology ,Research Article ,EXPRESSION ,Science ,EGFR ,education ,Socio-culturale ,03 medical and health sciences ,Diagnostic Medicine ,Carcinoma ,medicine ,Adenocarcinoma of the lung ,Cancer Detection and Diagnosis ,Humans ,030304 developmental biology ,Clinical Genetics ,Gene Amplification ,Chromosome ,Cancer ,Cancers and Neoplasms ,ADENOCARCINOMA ,IN-SITU HYBRIDIZATION ,medicine.disease ,Molecular biology ,3q chromosomal amplification ,Non-Small Cell Lung Cancer ,COPY NUMBER ,Chromosome 3 ,3111 Biomedicine ,Comparative genomic hybridization ,General Pathology - 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.
- Published
- 2012