Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study

• Published in: Radiation oncology (London, England) Vol. 6; no. 1; p. 161
• Main Authors: Molinari, Chiara, Ballardini, Michela, Teodorani, Nazario, Giannini, Massimo, Zoli, Wainer, Emiliani, Ermanno, Lucci, Enrico, Passardi, Alessandro, Rosetti, Paola, Saragoni, Luca, Guidoboni, Massimo, Amadori, Dino, Calistri, Daniele
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.11.2011; BioMed Central; BMC
• Subjects: Adjuvant treatment; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; ArrayCGH; Biomarkers, Tumor - genetics; Cancer; Care and treatment; Cell adhesion & migration; Cell cycle; Chemoradiotherapy, Adjuvant; Cloning; Cluster Analysis; Colorectal cancer; Comparative Genomic Hybridization; Diagnosis; DNA damage; Female; Fluorouracil - administration & dosage; Genetic aspects; Genetic variation; Genomes; Genomic alterations; Health aspects; Humans; Immunohistochemistry; Life sciences; Male; Middle Aged; neoadjuvant chemoradiotherapy; Neoadjuvant Therapy; Proteins; Radiation therapy; Radiotherapy; rectal cancer; Rectal Neoplasms - genetics; Rectal Neoplasms - therapy; Signal transduction; Statistical analysis; Studies; Surgery; Treatment Outcome; Italy
• ISSN: 1748-717X; 1748-717X
• DOI: 10.1186/1748-717X-6-161

Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies. Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade. Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions. This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients.The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].